Immunology Flashcards
Describe the difference between innate and adaptive immunity
Innate immunity = fast, short acting, non-specific, instinctive, present from birth, not dependent on lymphocytes
Adaptive immunity = slow, long acting, specific, acquired/learnt, regulated, requires lymphocytes
What are the progenitor cells of the innate and adaptive immunity?
Innate = myeloid progenitor
Adaptive = lymphoid progenitor
List the cells which are involved with the immune system
Neutrophil
Eosinophil
Basophil
Monocytes
T lymphocytes
B lymphocytes
Mast cells
Natural killer cells
Dendritic cells
Which cells are involved in the innate immune response?
Neutrophils
Eosinophils
Basophils
Monocytes (macrophages)
What cells are involved in the adaptive immune system?
Natural killer cells
T lymphocytes
B lymphocytes
Plasma cells
Describe the structure and role of neutrophils in the immune system
Tri-lobed nucleus, main phagocyte, principle cell of acute inflammation (IL-8)
What do eosinophils do in the immune system?
Stain pink, involved in allergic reactions
What do basophils do in the immune system?
Stain dark purple, involved in parasitic infections, release histamine on IgE crosslinking (like mast cells)
What is the structure and role of monocytes in the immune system?
Kidney-shaped nucleus, differentiate into macrophages in tissues, phagocytose and antigen present, principle cells in chronic inflammation
What do T and B lymphocytes do in the immune system?
T lymphocytes: can be T-regulators, T-helpers, or cytotoxic T cells
B lymphocytes: differentiate into plasma cells, produce antibodies
What do mast cells do in the immune system?
Involved in allergic reactions and parasitic infections, main source of histamine, activated by IgE crosslinking
What do natural killer cells do in the immune system?
Involved in viral infections and cancer, recognise non-self by MHCI receptors
What do dendritic cells do in the immune system?
Reside in the epithelium, phagocytose and antigen present, detect non-self by MHCII
What are the primary lymphoid organs?
Bone marrow (site of B lymphocyte maturation, and cell origin)
Thymus (site of T lymphocyte maturation)
What are the secondary lymphoid organs?
Lymph nodes (site of dendritic cells, B, and T lymphocyte interactions)
Spleen (removal of red blood cells and antibody coated bacteria, red pulp = vascular, white pulp = lymphoid aggregations)
What is complement and how does it act?
A group of 20 proteins secreted by the liver (need activating to function)
- direst lysis = e.g. membrane attack complex (MAC) puts hole in bacteria membrane
- chemotaxis = e.g. C3a and C5a cause phagocyte to migrate to bacteria
- opsonisation = e.g. C3b coats bacteria to make it easier for phagocyte to engulf
What does IgG do?
Most abundant, main antibody for secondary immune response, binds to phagocyte
What does IgM do?
Main antibody for primary response, immune memory, fixes complement
What does IgE do?
Binds to mast cells, eosinophils, and basophils, involved in allergic reactions and parasitic infections
What does IgA do?
Secreted in saliva, tears, mucous, tags pathogens for destruction
What does IgD do?
B cell receptor, stimulates the release of IgM
List the 5 classes of antibody
IgG
IgM
IgE
IgA
IgD
Describe the basic structure of an antibody
The basic structure for an antibody is a Y shape, with a common ‘F-c’ region which binds to receptors on immune cells, and 2 ‘F-ab’ regions which have a unique antigen binding site
List the cytokines which are involved in the immune system
Interferons (IFN)
Interleukins (IL)
Colony stimulating factor
Tumour necrosis factor (TFN)
Chemokines
What do interferons do?
Induce a state of antiviral resistance in uninfected cells close by to the infect cell
What do interleukins do?
There are many types, which can be pro-inflammatory (e.g. IL-1) or anti-inflammatory (e.g. IL-10)
They may also cause cells to divide, differentiate, or secrete different factors
What does colony stimulating factor do?
It directs the division of bone marrow stem cell (the precursors of leukocytes)
What does tumour necrosis factor do?
Mediates inflammatory and cytotoxic reactions
What do chemokines do?
They are secreted by cells (macrophages, lymphocytes, epithelial), and induce directional movement of leukocytes
List some physical and chemical barriers of the innate immune system
Skin: physical barrier, contains fatty acids and commensals
Gut: acidic conditions, rapid pH changes, contains commensals
Airways: muco-ciliary escalator removes pathogens, contains commensals
Vagina: low pH, contains commensals
What are commensals?
‘good bacteria’ which are needed to outgrow the ‘bad bacteria’
What are the three stages involved in the innate immune response?
Inflammatory response
Extravasation and recruitment of neutrophils
Phagocytosis
Describe the extravasation and recruitment of neutrophils as part of the innate immune response
- Macrophages at the site of infection release TNF-alpha which makes chemokines stick to the surface of the endothelium
- The endothelium becomes sticky so that neutrophils can roll along the surface
- Chemokines bind to chemokine receptors on the neutrophils, which causes them to transfer through the endothelial lining
- The neutrophils then migrate to the site of infection within the tissue
Describe the process of phagocytosis as part of the innate immune response
- A phagocyte (e.g. neutrophil) binds to the bacteria and engulfs it
- A phagosome forms and combines with a lysosome to form a phagolysosome
- The membrane of the bacteria is broken down by lytic enzymes or respiratory burst (oxygen radicals) to kill the bacteria
- Waste is removed, and a bacteria peptide is presented on the outside of the phagocyte (now an antigen-presenting cell, APC)
Describe the two sections the the adaptive immune response is split into
Cell-mediated response… uses T lymphocytes, against intracellular microbes
Humoral response… uses B lymphocytes, against extracellular microbes
What are major histocompatibility complexes?
MHCs are molecules on an infected cell which present the antigen peptide to be recognised by a T cell receptor
What does a class I MHC do?
Presents intrinsic antigens (from any cell) to cytotoxic T cells (CD8)
What does a class II MHC do?
Present extrinsic antigens (from antigen-presenting cells only) to helper T cells (CD4)
In the cell-mediated response, what does the recognition of ‘self’ and ‘non-self’ require?
Detecting the difference between intrinsic/endogenous antigens and extrinsic/exogenous antigens
The use major histocompatibility complexes
Describe the process of T cell antigen recognition and activation as part of the cell-mediated immune response
- T cell receptors bind to MHC (required for full T cell activation)
- This leads to division, differentiation, effector functions, and memory
- The activation is stimulated by the binding of IL-2 to receptors on T cells
- T cells can then be activated into cytotoxic T cells (Tc, CD8), helper T cells (Th, CD4), or regulator T cells (Treg)
Describe the role of cytotoxic T cells
They induce cell apoptosis of infected cells presenting MHC I
They release IFN for macrophage activation, and chemokines and TNF to recruit inflammatory cells
Describe the role of helper T cells
They recognise antigens on infected cells presented by MHC II
They secrete IFN to stop viruses spreading to neighbouring cells, and to activate macrophages
Describe process of B cell activation in the humoral immune response
- The B cell captures an antigen on membrane-bound antibodies (mIgR)
- The antigen is presented to Th2 cell, via MHC II, and the Th2 cell secretes interleukins
- These cause B cells to divide (clonal expansion) and differentiate into plasma cells or memory cells (Bm)
What is the role of plasma cells?
They produce antibodies which act on a specific epitope to neutralise toxins by binding to them, increasing opsonisation and phagocytosis, and activating complement
Define pattern recognition receptors
PRRs = a germline encoded receptors which detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)
What are toll-like receptors?
TLRs are present on the membranes of cells and detect a broad range or molecular patterns
Describe the roles of TLR2, TLR4, and TLR5
TLR2 = detects peptidoglycan PAMPs from gram +ve bacteria and lipopeptides
TLR4 = detects lipopolysaccharide PAMPs from gram -ve bacteria and viral proteins
TLR5 = detects flagellin PAMPs from flagellated bacteria
What are NOD-like receptors?
NLRs are cytosolic receptors that detect intracellular microbial pathogens
They trigger inflammation by recruiting and activating inflammatory caspases (or alternative routes)
Describe the use of NOD2
It is a widely expressed NLR which recognises a peptide which is a breakdown product of peptidoglycan from bacterial membranes, and activates inflammatory signalling pathways
Summarise the immunological theory
- An infection with an organism leads to the generation of protective substances in the serum,
-These are identified as circulating globulins (antibodies), which can neutralise and kill pathogens - Their protection persists (memory) and can be transferred to other subjects (passive immunity)
Define passive immunity
The transfer of pre-formed antibodies
Give an example of natural passive immunity
The transfer of maternal antibodies across the placenta to the developing foetus or through breast milk to new-borns
Includes protection against diphtheria, polio, tetanus, mumps, rubella, and whooping cough (vaccine given to mother’s to protect child)
Give an example of artificial passive immunity
Treatment with pooled normal human IgG or immunoserum against pathogens
- e.g. anti-toxins used to treat tetanus and diphtheria
- e.g. used prophylactically to reduce chances of established infection after exposure of hepatitis, rabies, measles
What are the disadvantages of passive immunity?
It doesn’t activate immunological memory
There is no long term protection
What is active immunity?
Manipulating the immune system to generate a persistent protective response against pathogens by safely mimicking natural infection
What is natural active immunity?
Naturally being exposed to and infected by the pathogen
What is artificial active immunity?
Vaccination
Describe the primary immune response created by a vaccine
After exposure to the antigen from the vaccine, the concentration of antibodies in the serum rises and falls shortly after
The reaction relies on the innate immune system and involves mostly IgM
It produces memory cells which circulate for years
Describe the secondary immune response after a vaccine
If a vaccine has been given, re-exposure with the antigen after some time will cause a rapid and powerful response
This mostly involves IgM, which will be present in very high levels
Somatic hypermutation can occur, where the antibodies adapt to new foreign elements
What is a live attenuated vaccine, give an example, and some +ves/-ves
A vaccine created by reducing the virulence of a pathogen but still keeping it viable (alive)
- e.g. tuberculosis-BCG
+ves = activates full natural immune response, provides prolonged and comprehensive memory
-ves = may infect immunocompromised, may revert back to virulent form
What is an inactivated vaccine, give some +ves/-ves
A vaccine which consists of pathogen particles grown in culture, which have lost their disease producing capabilities
+ves = no risk of infection
-ves = only activates a weak humoral response with no T cell involvement, requires boosters
Other than whole organism vaccines, describe three other types of vaccine design
Subunit vaccines = contains purified molecular components as immunogenic agents
DNA vaccines = transiently expresses genes from the pathogen in host cells to generate an immune response similar to a natural infection
Recombinant vector vaccines = imitate the effects of transient infection but using a non-pathogenic organism
What is a vaccine adjuvant?
Any substance which is added to the vaccine to stimulate the immune system
e.g. aluminium salts form precipitates and increase the effect of opsonised phagocytosis
Define hypersensitivity
Objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects, and may be caused by immunological (allergic) or non-immunological mechanisms
Describe a type 1 hypersensitivity reaction
e.g. allergy/anaphylaxis
IgE mediated
Occurs when IgE antibodies formed after exposure to a molecule become attached to mast cells and expressed as cell surface receptors, and re-exposure will cause mast cell degranulation releasing histamine etc.
Describe a type 2 hypersensitivity reaction
e.g. haemolytic reactions
IgG antibody cytotoxicity
The metabolite/drug combined with a protein and the body treats it as foreign so forms antibodies (IgG), which combine with antigens on the target cell surface and the cell is damaged by complement activation of cytotoxic T cells
Describe a type 3 hypersensitivity reaction
e.g. rheumatoid arthritis, glomerulonephritis
Immune-complex mediated
Antigens and antibodies form large complexes and activate complement, which damages/blocks small blood vessels, attracting leukocytes which begin the inflammatory process
Describe a type 4 hypersensitivity reaction
e.g. graft rejection, contact dermatitis, type 1 diabetes
Delayed hypersensitivity reaction, T lymphocyte mediated
Antigen specific receptors develop on T lymphocytes (Th1), activating cytotoxic T cells and macrophages, leading to local or tissue allergic reactions
Define allergy
An abnormal response to a harmless foreign material (allergens)
What are the clinical indications of allergy?
Skin = swelling, itchiness, redness
Airways = excessive mucus production, bronchoconstriction
GI = abnormal bloating, vomiting, diarrhoea
Anaphylaxis = ABCs
Describe the pathogenesis of allergic reactions
IgE acts as an antigen binding site to a specific allergen, and the crosslinking of the antigen to high affinity IgE receptors causes the cellular response of mast cells, basophils, and eosinophils
Describe the action of mast cells in an allergic reaction
Mast cells are the main effector cells in an allergic reaction, and when activated release histamine (causes vasodilation and bronchoconstriction), cytokines, proteases, and proteoglycans in an immediate reaction, and leukotrienes, prostaglandins, and platelet aggregating factors in a later response
What makes something an allergen?
The presence of weak PAMPs, leading to a weak innate immune activation (Th2 cells)
Describe some allergic disease
Anaphylaxis = involves mast cell or basophil activation, causing rash, bronchoconstriction, and shock
Allergic asthma = triggered by house dust mite faeces, aspergillus etc., eosinophils influx into lungs, involves IgE
Chronic asthma = type 4 hypersensitivity reaction, caused by problem with regulatory T cells which control eosinophil responses (overactive)
Describe some treatment strategies for allergic diseases
Avoid allergens
Desensitisation to allergen (immunotherapy, moderate risks)
Prevent IgE production (supressing Th2 response)
Prevent IgE interaction with receptor
Prevent mast cell interaction (anti-cytokine antibodies)
Inhibit mast cell products
