Haem - Immunology Flashcards
Define antigen
A substance that stimulates the immune system resulting in an immune response.
The immune system produces antibodies to the atigen
What type of molecules can antigens be
Proteins or polysaccharides
Define a hapten
A hapten is a small molecule that may also stimulate the immune system, but only when attached to a large carrier protein.
The immune system produces antibodies to the hapten-carrier complex.
These antibodies can also bind to the hapten when not bound to the carrier protein
Define allergen
An environmental antigen that produces a vigorous immune response, even though the allergen is usually harmless.
List the components of the innate immune system
- Anatomical/physiochemical
- Skin
- Mucociliary escalator
- Low gastric pH
- Peristalsis (bile/GIT)
- Lysozyme saliva and tears (bact. cell wall lysis) - Inflammation
- Complement System
- Cellular
- PMNs, Macrophages, NK, Mast, Eosin, Basophil) - Acute Phase Proteins
- CRP, alpha antitrypsin
List the components of the adaptive immune system
Cell mediated immunity
- Cytotoxic T-cells
- Defence against intracellular pathogens and abnormal host cells.
Humoral (Antibody - mediated) immunity
- B cells
- T-helper cells
- Defence against pathogens within body fluids
Name the predominant leucocyte and describe its function
Neutrophil (60% of all leucocytes)
- Phagocytosis bacteria and fungi
How many bacteria can a neutrophil phagocytose before it dies
5 - 20
What is the difference between a neutrophil and a macrophage
Macrophage can phagocytose up to 100 bacteria before it dies (vs. neutrophil: 5 - 20)
Furthermore, Macrophages also phagocytose cellular debris
What is the function of eosinophils
Killing multicellular organisms such as helminths and parasites.
Important (along with mast cells) in the pathogenesis of allergic reactions and asthma (eosinophil count high in both conditions)
What are basophils and what is their function
Least common of all the leukocytes
Act like circulating mast cells
Have granules: histamine and heparin
Involved in allergic reactions and defence against parasites
What are NK cells. What is their function
Classed as lymphocytes but unlike other lymphocytes are non-specific in their immune function.
Function: Very important
- Destroy tumour cells
- Destroy cells infected with viruses
- Role in suppression of maternal immune system vs. fetus in pregnancy
What is inflammation
Non-specific response triggered by either micro-organism invasion or tissue injury
- Vasodilation (redness/heat)
- Vascular permeability increased (swelling)
- Migration phagocytes
How do trauma and infection initiate the inflammatory response?
Trauma
- Mechanical damage –> mast cell degranulation –> release of histamine + inflammatory cytokines
- Blood vessel disruption –> activates plts and coagulation cascade
Infection
- Tissue macrophages recognize and phagocytose micro-organisms –> Release pro-inflammatory CK: IL-1, IL-6, TNF alpha –> trigger mast cells to degranulate –> more pro-inflammatory cytokines released.
Differentiate the local from the systemic inflammatory response
LOCAL
VD
–> increase local blood flow
Increased capillary permeability
–> Plasma / complement / coagulation proteins / antibodies move into interstitium
Recruitment of immune cells
–> Endothelial cells express cell surface adhesion molecules –> slow down circulating macrophages and neutrophils, allowing them to pass between the endothelial cells (transmigration)
–> Thereafter, the leucocytes are are then guided toward the site of infection.injury by attractants called chemotactic molecules
SYSTEMIC
Severe inflammation or micro-organism escapes the site of invasion –> systemic inflammation.
Systemic Cytokines
1. Fever (Augments phagocytosis and impairs bacterial multiplication)
2. Release of neutrophils from bone marrow
3. Release of acute phase reactants (CRP)
What is ‘transmigration’?
Inflammatory cytokines–> Endothelial cells express cell surface adhesion molecules –> slow down circulating macrophages and neutrophils, allowing them to pass between the endothelial cells
How do phagocytes move from blood to the site of infection
Via transmigration followed by chemotaxis
What are Eicosanoids. What are Kinins.
EICOSANOIDS
- Family of signalling molecules
- Pro-inflammatory cytokine
- Derived: Arichidonic Acid
- Subclassified
- -> Prostaglandins
- -> Prostacyclins
- -> Thromboxanes
- -> Leukotrienes
KININS
- Poorly understood
- Produced during inflammation by cleavage from inactive precursor
- E.g.Bradykinin
- -> Arteriolar vasodilation
- -> Increase permeability of post capillary venules
- -> Sensitization nociceptors
What are the components and function complement system
Collection of 25 plasma proteins which ‘complement’ the activity of antibodies.
FUNCTIONS
- Bacterial cell lysis
- Membrane attack complex (mulitple proteins together) –> H2O moves in through holes in cell membrane –> swelling and bursting of bacterial cell - Opsonization for phagocytosis efficiency
- Coat surface of m/o to bind PMNs and Macrophages - Chemotaxis
- Honing beacons, guiding leucocytes toward site of infection. - Triggering local mast cells to degranulate
- Augmenting inflammatory response
What is lymphoid tissue
Collective term for tissue that:
- Produce lymphocytes (bone marrow)
- Process lymphocytes (thymus)
- Store lymphocytes (Lymph nodes, spleen, tonsils, appendix, GIT Peyer’s Patches)
Where do B cells and T cells named B and T cells
According to the place that these cells mature.
B cells - mature in the bone marrow
T cells - mature in the Thymus
What is DiGeorge Syndrome
Genetic disorder –> Results in a midline congenital defect.
CATCH 22
Cardiac defect (Interrupted aortic arch) Abnormal facies Thymus Aplasia Cleft Palate Hypocalcaemia / Hypoparathyroidism
22 - Defect chromosome 22q11
Why is the thymus important in T cell maturation
The thymus is able to synthesize and express all the proteins of the body educating the T-cells about self vs. non-self.
T-cell receptor proteins are generated at random.
Any T-cell that interacts strongly with a host protein is eliminated by apoptosis in the thymus.
Thymus induced T-cell apoptosis results in elimination of what proportion of immature T cells
98% –> Only 2 % remain to survive to full maturation.
Where are B cells tested for reactivity against self?
In the bone marrow. B cells that react to self are eliminated in the bone marrow via apoptosis.
What are antibodies. List the function of antibodies
Antibody or immunoglobulin is a Y shaped protein produced by the adaptive immune system. Antibodies bind to specific pathogens and have the following functions:
- OPSONIZATION
- Label pathogens allowing for easier identification by leucocytes (Fc region) - AGGLUTINATION
- More than one binding site for pathogens clumping them together –> bigger targets for leukocytes - INACTIVATION of pathogen (if binding site NB in pathogen function or toxin binding)
- Activation of COMPLEMENT
- opsonization / chemotaxis / mast cel degranulation / membrane attack complex
List the steps and factors involved in the mass production of a highly specific antibody
- Phagocytosis of antigen by APC
- APC presents Ag on cell sruface and goes to lymph node
- Ag presented to multiple immature B and T helper cells until the appropriate binding occurs.
- Clonal expansion of activated specific T helper cell + memory T helper cell
- Clonal expansion of activated plasma cell + memory B cells.
- Plasma cells mass produce Ag specific antibodies
What are Antigen Presenting Cells: APCs
APCs are Macrphages and Dendritic cells that phagocytose bacteria and present the bacterial Ag on the cell surface for immature T helper and B cell recognition.
What is a Major Histocompatibility Complex MHC
The class II MHC is a large protein on the surface of Antigen Presenting Cells that display the Antigen of the phagocytosed micro-organism.
What is another name for T helper cells and why
CD4+ cells as it is the T-cell CD4+ receptor that interacts with the APC MHC class II molecule
How many antibodies can a plasma cell make per second? How long to plasma cells survive
2000
so committed to Ab production that they do so at the detriment for normal cellular function and only survive for about 1 week
What is the difference between the primary and secondary immune response
PRIMARY IMMUNE RESPONSE
- Pathogen invasion –> Antibody production takes 5 DAYS
- Main Ig produced IgM, then IgG later
- Most plasma cells and T-helper cells die within the next 5 days after the pathogen has been destroyed
SECONDARY IMMUNE RESPONSE
- Re-invasion by same pathogen
- Faster and more vigorous
- Memory T-helper and B cells activated
- Antibodies produced within HOURS of infection
- IgG mainly produced (minimal IgM)
- Pathogens can be killed before they make the host ill
What is active immunity
Where a person is immune from a particular infection as a result of previous exposure
What is the difference between active and passive immunization
ACTIVE immunization
- Vaccine (inactive pathogen administered to patient)
- Antibodies and memory Th and B cell produced
- Subsequent exposure = rapid secondary immune response occurs
PASSIVE immunity
- Pre-formed antibodies are given to patient
1. Physiological - IgG across placenta
- IgA via breastmilk
- Clinical
- Recombinant Ab given to neutralize pathogen or toxin
E.g. Varicella Zoster Ig (At risk pregnant patients)
E.g. Tetanus Ig (neutralize tetanus toxin in severe tetanus)
What are the steps and factors involved in cell mediated immunity
Intracellular pathogens (viruses, parasites, yeasts and some bacteria) hide in the bodies own cells, where they grow and manipulate the cell’s protein synthesis and replicate.
- All cells programmed to express samples of IC proteins on their surface
- Patrolling Cytotoxic CD8+ T cells recognize non-self antigens expressed on cell’s surface
- CD8+ interacts with MHC class 1 molecule
- Cell apoptosis then occurs in host cell
- Macrophages phagocytose dead host cell
- Activated cytotoxic CD8+ cell rapidly divides to search for more infected cells
This includes cancer cells with abnormal surface proteins
What is intracellular antibody-mediated degradation
IgG binds to virus/bacterium which then infects a cell with Ab still bound. Inside the cell the Fc component of the IgG is directed to the proteosome by a protein called TRIM21 where the pathogen-IgG complex is degraded.
What is Fab and Fc on an antibody
Fc is constant and the same on all types of antibodies. It is the portion of the antibody that binds immune system parts e.g. phagocytes and complement.
Fab - Area that recognises and binds antigen.every Ab has a different Fab
Describe the structure and defining characteristic of the five types of antibodies
IgM - Aggregate of 5 ‘Y’ subunits (Large and 1st Ab produced in the primary immune response
IgG - Single ‘Y’. Only Ig that can cross the placenta
IgA - Dimer of ‘Y’ ig. Found in mucosa (RSP, GIT), saliva, tears, breast milk
IgE - Monomer ‘Y’ Ig. Found on mast cells. Ag binds IgE –> Mast Cells degranulate = type 1 hypersensitivity
IgD monomer ‘Y’ Ig. attached alongside IgM to the cell membrane of naive B cells. ? purpose yet discovered.
Classify immunodeficiency
PRIMARY (Defect in immune system development) - T cell dysfunction(e.g. DiGeorge) - T and B cell dysfunction (Severe combined immunodef) - B cell dysfunction - Complement deficiency
SECONDARY
- Iatrogenic: Steroids / chemo / DXT / Immunosupressive drugs
- Ageing/Malnutrition
- Specific diseases: Leukaemia/Myeloma/AIDS
Define hypersensitivity. What are the 4 types of hypersensitivity
Definition: Exaggerated or inappropriate immune response that causes discomfort, tissue damage or even death.
Type 1 - Immediate
Type 2 - Cytotoxic
Type 3 - Immune complex disease
Type 4 - Delayed-type
What is type 1 hypersensitivity. Give 3 examples
IMMEDIATE HYPERSENSITIVITY (IgE)
- 1st allergen exposure: Th + B cells produce IgE which coat mast cells
- Re-exposure to an allergen –> rapid degranulation –> histamine, PGs, leukotrienes
- Clinical effects depend on location of mast cells and route of allergen entry
E.g.
- Anaphylaxis
- Allergens reach systemic circulation
- Widespread mast cell degranulation
- VD, BS, Fluid extravasation - Asthma
- IgE-Mast cell in bronchioles
- BS, fluid extravasation - Allergic rhinitis (hay fever)
- Ige-mast cell in mucosa nasopharynx
- itchy eyes/ inflamed nasal mucosa / mucus
What is type 2 hypersensitivity. Give 2 examples
CYTOTOXIC HYPERSENSITIVITY (IgG)
- Ab binds own cells. Ab - Ag complex triggers complement –> initiates inflammation and facilitates phagocytosis by macrophages.
E.g. ITP - Idiopathic thrombocytopaenic Purpura
- IgG coat platelets + megakaryocytes –> phagocytosis by splenic and hepatic macrophages
E.g. Goodpastures disease
- IgG binds type IV collagen of basement membrane in renal glomerulus and pulmonary alveolus –> AKI + pulmonary haemorrhage.
What is type 3 hypersensitivity. Give 2 examples
IMMUNE COMPLEX DISEASE (usually IgG)
- Ab - Ag complexes insufficient in number to activate complement. Complexes lodge in small blood vessels, joints, glomeruli –> inflammation.
E.g. SLE (Antinuclear antibodies)
E.g. Farmer’s lung (hypersensitivity pneumonitis: inhaled mould spores trigger Ab production - Ab - Ag deposit in lungs causing inflammation.
What is type 4 hypersensitivity
DELAYED - TYPE HYPERSENSITIVITY (No Ab)
- Some allergens trigger a type of hypersensitivity that involves T cells, not Ab.
- slower: takes 2 - 3 days
- Th cells: divide and secrete cytokines which activate macrophages which cause cell damage
E.g. Tuberculosis
–> Activated macrophages fuse to form giant cells around the TB antigen –> necrotic centre (caseating granuloma)
E.g. Contact dermatitis
–> Contact with certain allergens causes a delayed reaction (e.g. nickel)
What are the most common precipitants of anaphylaxis in the perioperative period?
- Muscle relaxants (60% of cases)
- Antibiotics (peniciliin NB) (15% of cases)
- Dyes (Patent Blue and Methylene blue)
- Antiseptics (Chlorhexidine and Povidine)
- Colloids (Gelatins)
- Iodinated contrast media
- Sugammadex
- Ester local anaesthetics (Cocaine / Procaine / Amethocaine)
- Propofol / opioids
How is the immune system depressed in the perioperative period
- STRESS RESPONSE of surgery: impaired lymphocyte function and phagocytosis
- VOLATILE: Impaired neutrophil phagocytosis (PMNS)
- PROPOFOL/THIOPENTONE: Impair MP and PMN phagocytosis
- OPIOIDS: Impair PMN, MP, NK, lymphocyte proliferation and cytokine release.
(NK cells particularly NB as they kill stray tumour cells that evade surgery) - TRANSFUSION RELATED IMMUNOMODULATION (TRIM). Allogenic blood transfusion causes a temporary depression of the immune system (useful in transplants but may increase cancer recurrence in cancer surgery)
- PERIOPERATIVE HYPOTHERMIA
- depresses both innate and adaptive immune system –> may reduce survival in cancer surgery
What is TRIM. When is it advantageous and when is it disadvantageous
Transfusion related immunomodulation
Allogenic blood transfusion causes a temporary depression of the immune system.
Advantageous: Transplant surgery
Disadvantageous: Cancer surgery
