Immunology Flashcards
What is an antigen?
Substance that stimulates the immune system, resulting in an immune response - Proteins or polysaccharides
What is a hapten?
Small molecule that may also stimulate the immune system, but ONLY when attached to a larger carrier protein
What is an allergen?
Environmental antigen that produces a vigorous immune response, even though the allergen is usually harmless
What is inflammation?
Non-specific response triggered by either microorganism invasion of tissue injury
Innate Immunity
- First line of defence - always active
- Fast acting - min to hours
- No specificity, no memory, no improvement with repeat exposure
- Physical - skin/mucous membranes, provides physical resistance to entry, secrete antibacterial substance
- Chemical - provide hostile environments, mucous and cilia, gastric acid, urine flow
- Humoral
=> Inflammation - aids to remove injurious stimuli and initiate healing. Dilation and increased permeability of capillaries (mediated by bradykinin, HA, PG). Endothelial activation (adhesion of WBC). Attraction and activation of neutrophils
=> Fever - creates hostile environment, incr body metabolism and CVS response to mobilise immune cells
=> Humoral components - complement, acute phase proteins, proteolytic enzymes (lysozymes), inflammatory cytokines - Cellular (phagocytes + NK cells)
Complement
- Defend mainly against bacteria
- Inhibition by regulator proteins (C1 esterase inhibitor)
- Anti-infective - activate neutrophils and phagocytes, lysis of bacteria/ foreign cells
=> Opsonisation C3b
=> Chemotaxis C1-4 and C5a - Immune signalling - immunomodulate B cell response to antigens, mast cell degranulation
- Clearance - clear immune complexes and apoptotic cells via C1q, C3, C4
Classical pathway (part of adaptive immune system)
- Activated by IgG or IgM antigen complex
- Initiated when C1q bind Fc portion of Ig
=> C1 and C4 activate C2 (classic pathway) - activates C3
- Forms C3 convertase
Alternative pathway (Part of innate system)
- Initiated by C3 activation (formation of C3 converts)
- Continuous low level activation due to thioester hydrolysis of C3
- Occurs in fluids or on contact with foreign surfaces
Lectin pathway (Part of innate system)
- Initiated by mannose binding lectin (MBL)
- Binds CHO on bacteria, fungi and viruses and activates C4 and classic pathway
Final common pathway
- C3 activation key even of classic and alternate pathway
- C3 cleaves C5 into C5a + C5b
- C5b combine with C6, C7, C8 + C9 to form membrane attack complex (MAC) that damages cell membranes
- Exerts effects of complement system
=> Membrane pore => lysis
=> Opsonisation for phagocytosis by neutrophils and macrophages
=> Chemotaxis
=> Mast cell degranulation
Adaptive Immune System
- Slower response, but specific
- Have advantage of ‘memory’ - much quicker response occurs if the same micro-organism invades for a second time
- Involvement of both cellular and humoral elements - cytotoxic T-cells (cellular); B-cell and T-helper cells for antibody mediated (humoral)
Antibody
- Y shaped protein produced by the adaptive immune system
- Consist of 2 identical heavy chains and 2 identical light chains, linked by disulphide bridges
- Have two regions
=> Variable region, Fab - recognises and binds antigens. Every antigen has a different Fab
=> Constant region, Fc - area that binds to other parts of the immune system, such as phagocytes and complement. Each different type of Ig (i.e IgG, IgM etc) has an identical Fc.
Functions:
- Opsonisation
- Agglutination
- Inactivation of pathogen
- Activation of complement
Types
- IgM - largest Ig, consisting of an aggregate of five ‘Y” Ig subunit. First type of antibody produced in the primary immune response and is good at binding large antigens.
- IgG - most abundant Ig. Composed of single ‘Y’ Ig and is the only Ig that can cross the placenta
- IgA - dimer of ‘Y’ Ig. Found in the mucosa, saliva, tears and breast milk
- IgE - monomer Ig found on the surface of mast cells. When an antigen binds to IgE, the mast cell is triggered to degranulate. Mechanism of type I hypersensitivity. Normally present in low conc, but may incr with atopy, parasitic infection and hypersensitivity
- IgD - monomer Ig, usually attached alongside IgM to the cell membrane of naive B cells. IgD disappears once B cell activated, when it becomes entirely covered with IgM.
Active vs passive immunisation
Active
- Inactive portion of virus/ bacteria given to patient
- Patient’s immune system produces antibodies to the antigen, during when memory B and TH cells are produced
- If subsequently exposed to active pathogen, rapid secondary immune response occurs
Passive
- Preformed antibodies are given to patient
- Physiological - Antibodies (IgG) transferred across placenta from mother to foetus. After birth, antibodies (IgA) also transferred through breast milk
- Clinical - recombinant antibodies can be given parenterally to a patient to neutralise a pathogen or toxin. E.g varicella zoster Ig, tetanus Ig
T-cells
Helper T-cells
- 2/3 of T-cells
- Surface glycoprotein CD4, and recognises antigens that express MHC Class II molecules on APCs
- Functions - release cytokines and activate macrophages, stimulates B-cells to form plasma cells and antibodies
- Subcategory
=> TH1 - promote cell mediated/ inflammatory immune responses by activating cytotoxic T-cells, NK cells and macrophages
=> TH2 - promote antibody production by B-cells
Cytotoxic T-cells
- 1/3 of T-cells
- CD8 surface glycoprotein and interact with MHC class I molecules
- Kills cells by perforins into target cell membranes through which granzyme inserted => osmotic lysis of cell or induce aptosis
- Used in controlling viral infections and cancers
Hypersensitivity
- Exaggerated or inappropriate immune response that causes discomfort, tissue damage or even death
Type I/ immediate hypersensitivity
- Primary exposure to antigen -> B lymphocytes produce specific IgE -> IgE binds to Fc receptors on mast cells -> mast cells sensitised -> re-exposure to the antigen -> the antigen binds to IgE -> degranulation of mast cells -> release of inflammatory mediators (e.g HA, 5HT, kinins, PGs)
- E.g asthma, allergic rhinitis, anaphylaxis
Type II/ cytotoxic hypersensitivity
- IgG or IgM bind to cell surface antibodies -> complement activation via classical pathway -> cell lysis, phagocytosis, inflammation
- E.g haemolytic transfusion reaction, heparin induced thrombocytopenia, Goodpasture’s disease
Type III/ immune complex disease
- Deposition of antigen-antibody complexes in target tissues -> complement activation
- E.g serum sickness, SLE, Farmer’s lung
Type IV/ delayed
- Antigen presentation to T-lymphocytes -> release of cytokines -> activation of macrophages -> tissue damage
- Requires 24hrs to reach max effect
- E.g contact dermatitis, TB
Immune consequences of anaesthesia and surgery
Disruption of physicochemical barriers
- Surgery where skin or mucosa breaches
- ETT - breathing dry air inhibits ciliary function in tracheobronchial tree, predisposing to pneumonia
Exposure to allergens
- Muscle relaxants
- Abx
- Antiseptics
- More rarely - latex, colloids, blood products, amide LAs, induction agents
Depression of immune system
- Stress response to surgery
- Opioids - impair macrophage, neutrophil, NK cell function, lymphocyte proliferation and cytokine release
- Volatiles - reduce NK cell function
- TIVA - ?reduce cancer recurrence
- Transfusion related immunomodulation - allogenic blood transfusion causes temp depression of immune system
- Perioperative hypothermia - depresses innate and immune systems
Serum tryptase
- 1st sample as soon as practical
- 2nd sample at 4hrs
- 3rd sample >24hrs
