IMMUNOLOGY Flashcards
- Innate Immune system - Adaptive Immune system - Autoimmunity - Allergy and Hypersensitivity - Vaccination - Immunodiagnostics
What are the differences between the innate and adaptive immune response?
Innate immunity is non-specific and has no memory
Adaptive immunity is specific, systemic and has memory
What are the two external defences of innate immunity?
Skin
Mucous membranes
What are the four internal defences of innate immunity?
Inflammatory response
Complement proteins
Phagocytic cells
Natural killer cells
List the eight cell types involved in the innate immune system
Neutrophils
Eosinophils
Basophils
Mast cells
Monocytes
Macrophages
Dendritic cells
Natural killer cells
List the three types of phagocytic cells
Neutrophils
Macrophages
Dendritic cells
List the antigen presenting immune cells
Macrophages
Dendritic cells
B-lymphocytes
What is antigen presentation?
The process by which an MHC molecule binds to an antigen fragment and carries it to the cell surface, where it is displayed and can be recognised by T-lymphocytes
Where do mast cells reside within the body?
In the connective tissues and mucous membranes
Where do dendritic cells reside within the body?
In the skin and mucous membranes
What is the complement cascade?
The complement cascade is a series of cleavable plasma proteins circulating the bloodstream
What are the two main methods of complement cascade activation?
Binding of complement proteins to microbial cell walls or to antigen-antibody complexes
Describe the process of the complement cascade
- Activation of complement by the presence of microbial cell walls or antigen-antibody complexes stimulates the cleavage of C3 into C3a and C3b
- Further down the cascade, C5 is cleaved into C5a and C5b
- C3a and C5a amplify the inflammatory response and chemotaxis
- C3b coats pathogens to induce phagocytosis by phagocytic cells
- C5b induces the membrane attack complex
What is the membrane attack complex?
A series of perforin proteins which form pores in the pathogen cell membrane, causing the pathogen to lyse
What is the function of natural killer cells?
Natural killer cells recognise and kill neoplastic and virally infected cells through the release of granules containing perforin which forms pores within the cell membrane to allow granzymes to move into the abnormal cell to induce apoptosis
What are the two divisions of the adaptive immune response?
Humoral immunity
Cell-mediated immunity
List the cells and proteins involved in the adaptive immune response
B-lymphocytes
T-lymphocytes
Antibodies
Where in the body do lymphocytes circulate?
Very small numbers in the blood circulation
Tissues
Lymphatic system
What are exogenous invaders and which division of the adaptive immune response do they stimulate?
Exogenous invaders are organisms that originate outside of the body which stimulate the humoral immune response
What are endogenous invaders and which division of the adaptive immune response do they stimulate?
Endogenous invaders are organisms within the host cells which stimulate the cell-mediated immune response
What is humoral immunity?
Humoral immunity is the aspect of the immune system mediated by antibodies and B-lymphocytes
What are antigens?
Antigens are immunogenic foreign molecules which are the targets of the adaptive immune response
What region of antigens is bound to by antibodies?
Epitope
List the five basic structures found in antibodies (immunoglobulins)
Heavy chain
Light chain
Variable domain
Constant domain
Hinge region
What are the four functions of antibodies?
- Antibodies bind to specific antigens, tagging pathogens for phagocytosis
- Antibodies undergo opsonisation
- Antibodies neutralise pathogens through binding to and blocking the pathogen’s binding sites, preventing the pathogen from binding to tissues
- Antibodies trigger complement proteins
What stabilises the light and heavy chain that makes up antibody proteins?
Disulphide bonds
What are the three functions of the constant domain (Fc region) of antibodies?
- The amino acid sequence of the constant domain determines the antibody classification
- Region that binds to phagocytic cells
- Region that binds to and triggers complement
What is the function of the variable domain (Fab region) of antibodies?
The site that binds to specific antigen epitopes
What is idiotypic immunoglobulin variation?
Variation in the antigen binding (Fab) region of the antibody
What is isotopic immunoglobulin variation?
Variation in the types of light and heavy chains that make up the antibody
What is allotypic immunoglobulin variation?
Variation in the amino acid sequences of the light and heavy chains that make up the antibody
List the six different antibody classifications
IgM
IgG
IgA
IgE
IgD
IgY
Describe IgM antibodies
- Pentamer structure joined by a polypeptide J-chain
- First antibody produced in response to an antigen
- Low affinity, high avidity
- Efficient at binding to pathogens with repeating epitopes on their surface
Describe IgG antibodies
- Monomer structure
- Most abundant antibody in the blood and lymph
- Binds to the Fc receptors on phagocytic cells
- Triggers complement
- Only antibody that can pass thorough the placenta to provide foetal passive immunity
Describe IgA antibodies
- Dimer structure joined by a polypeptide J-chain
- Most abundant antibody in bodily secretions
- Fc receptors of neutrophils and macrophages have a high affinity for IgA receptors
- Efficient at binding to pathogens with repeating epitopes on their surface
Describe IgE antibodies
- Monomer structure
- Fc receptors of mast cells have a high affinity for IgE
- IgE triggers mast cell degranulation resulting in the release of histamine
Mast cell Fc receptors can bind to IgE antibodies even when the antibody isn’t bound to an antigen. Explain why this is the case
Mast cell Fc receptors can automatically bind to IgE receptors to allow the instant degranulation of these immune cells in response to invading parasites
Describe IgD antibodies
- Monomer structure
- Present on the surface of B-lymphocytes during their development
Describe IgY antibodies
- Monomer structure
- Only found in birds
- Combination of IgG and IgE function
What is passive immunity?
The immunity one organism gains from receiving the antibodies from another organism that already has immunity
Which antibodies can be passed through colostrum to provide neonates with passive immunity?
IgG, IgM, IgA
Which animals gain passive immunity from colostrum?
Equine
Ruminants
Porcine
Canine
Feline
Which animals gain passive immunity through antibodies being passed through the placenta?
Canine
Feline
Where are B-lymphocytes produced and matured?
Bone marrow
Describe the positive selection stage (somatic hypermutation) of B-lymphocyte maturation
As B-lymphocytes mature, they develop immunocompetence (the development of antigen specific antibodies). Immunocompetence is achieved via positive selection which involves antibody heavy chain VDJ recombination, producing unique variable domains in each antibody for specific antigen binding
Describe the negative selection stage (central tolerance) of B-lymphocyte maturation
As B-lymphocytes develop, they develop self-tolerance (the ability to recognise self-antigens). Self-tolerance is achieved via negative selection where B-cells with antibodies with a high affinity for self-antigens will be destroyed by clonal deletion
Where are B-lymphocytes activated?
Secondary lymphoid tissues (mainly lymph nodes)
Describe the activation and clonal proliferation process of B-lymphocytes
Naive B-lymphocytes are activated when the unique B-lymphocyte antibodies bind to their specific antigens present in the secondary lymphoid tissues. Activated B-lymphocytes undergo clonal proliferation where these B-lymphocytes and their specific antibody will be differentiated into plasma cells and memory B-lymphocytes
What is the function of plasma cells?
Plasma cells secrete antigen specific antibodies into the blood and the lymph
Which classification of antibody is produced first by plasma cells in response to a foreign antigen?
IgM
Which process allows plasma cells to produce other antibodies classifications in response to secondary antigen exposure?
Helper T-cells initiate isotype switching of plasma cell antibodies
What is the function of memory B-lymphocytes?
Memory B-lymphocytes remain dormant until reactivated by a specific antigen which will stimulate plasma cell production and thus mass antibody production
What is peripheral tolerance?
Peripheral tolerance is the inactivation of self-selective B and T-lymphocytes that have managed to enter the periphery
Where are T-lymphocytes produced?
Bone marrow
Where are T-lymphocytes matured?
Thymus
Describe the positive selection stage of T-lymphocyte maturation in the thymus
Double positive thymocytes (CD4+, CD8+) are presented with self-antigens bound to MCH class 1 and MHC class 2. Thymocytes which do not bind to MHC are destroyed by apoptosis
Describe the negative selection (central tolerance) stage of T-lymphocyte maturation in the thymus
Positively selected thymocytes are re-presented with self antigens bound to MHC class 1 and MHC class 2. Thymocytes which interact too strongly with the self antigens presented on MHC will undergo apoptosis
What is the major histocompatibility complex (MHC)
The major histocompatibility complex (MHC) are proteins found on the surface of cells which bind to antigen fragments, allowing T-lymphocytes to recognise self-cells from non-self cells
Which cells present MHC class 1 proteins?
MHC class 1 is a surface protein presented on all healthy nucleated cells (each cell has a unique MHC class 1 protein)
Which cells present MHC class 2 proteins?
MHC class 2 is a surface protein presented on antigen-presenting cells
Where are T-lymphocytes activated?
Secondary lymphoid tissues (mainly lymph nodes)
Describe T-lymphocyte activation and clonal proliferation
Naive T-lymphocytes are activated when specific T-cell receptors bind to specific antigens bound to MHC proteins
Naive T-lymphocytes with CD4+ receptors bind to specific antigens presented on MHC class 2 proteins, causing clonal proliferation of helper T-lymphocytes
Naive T-lymphocytes with CD8+ receptors bind to specific antigens presented on MHC class 1 proteins, causing clonal proliferation of cytotoxic T-lymphocytes
What are the three functions of helper T-lymphocytes?
- Proliferation of memory T-lymphocytes and regulatory T-lymphocytes
- Cytokine secretion which can activate more cytotoxic T-lymphocytes
- Stimulation of plasma cell isotype switching
What is isotype switching?
Initially plasma cells produce IgM antibodies. When IgM antibodies bind to an antigen, this antigen will be presented on MHC class 2 to helper T-lymphocytes. CD4+ receptors on the helper T-lymphocytes will bind to the antigen, secrete cytokines, resulting in isotype switching of the plasma cells. Isotype switching results in these plasma cells changing which type of antibodies they produce through recombination of the constant domain (Fab region) of the antibody
What is the function of cytotoxic T-lymphocytes and how do they carry out this function?
Cytotoxic T-lymphocytes kill viral and neoplastic infected cells through binding to specific antigens presented on MHC class 1 proteins bound to the abnormal cell. Cytotoxic T-lymphocytes will release perforin which creates pores in the abnormal cell to allow the movement of granzymes into the cell to induce apoptosis
Describe the effects of primary vaccination on antibody production
Primary vaccination initiate the production of IgM and IgG antibodies at a low titre
Describe the effects of secondary vaccination (boosters) on antibody production
Secondary (booster) vaccinations initiate the production of high titre, high affinity IgG
List the three different types of vaccine currently available
Killed/inactivated vaccines
Live attenuated vaccines
Subunit vaccines
What are killed/inactivated vaccines?
Vaccines derived from killed/inactivated viruses
What are the five disadvantages of killed/inactivated vaccines?
- Hazardous to the personnel working to grow and kill/inactivate the virus
- Hazardous to animals if the virus is accidentally released into the environment
- The virus HAS to be 100% inactivated
- More than one injection is required due to the short lived response of the antibody produced
- Conformational epitopes of the viral antigen are often denatured during the killing/inactivation process
Why do killed/inactivated vaccines have such a short lived antibody response?
Because the virus is inactivated/killed, so the antigen levels within the host don’t persist leading the antibody response to be short lived
What are live attenuated vaccines?
Vaccines derived from a live virus that has mutated so that it is no longer pathogenic
What are the advantages of live attenuated vaccines?
- Antigen levels persist, allowing for a prolonged antibody response
- The virus can be exogenous and endogenous, stimulating the humoral and cell-mediated immune response
- Conformational epitopes of the viral antigen will remain intact
What are the disadvantages of live attenuated vaccines?
- The live virus can be contaminated during production
- Limited shelf life
- Risk of reversion to virulence/side effects
What are subunit vaccines?
Vaccines derived from viral antigenic fragments
What are adjuvants?
Adjuvants can be added to vaccines to non-specifically enhance the immune response through inducing an inflammatory response
What is autoimmunity?
Autoimmunity is the action of the immune response against self antigens/cells
How does autoimmunity arise?
Due to the failure of the central and peripheral tolerance systems
What are the two mechanisms by which central tolerance can fail?
- If MHC inappropriately or doesn’t express self antigens during the negative selection stage of T-lymphocyte maturation
- If weakly self-reactive T and B-lymphocytes survive negative selection in the primary lymphoid tissues
What is polyclonal activation and how can this cause autoimmunity?
Polyclonal activation is the clonal proliferation of B-lymphocytes with antibodies which can bind to multiple different epitopes (including epitopes of self-antigens)
What is an allergy?
An abnormal hypersensitivity where the immune system causes tissue damage in response to a harmless or self-antigen
What is the term used for antigens that induce allergic reactions?
Allergens
What is the cause of type one hypersensitivity?
The binding of allergens to IgE antibodies bound to mast cells, stimulating the degranulation of the mast cells and the excessive release of histamine
How does excessive histamine release result in tissue damage?
Histamine binds to H1 receptors on the smooth muscle and endothelial cells, resulting in bronchoconstriction, vasodilation and increased capillary permeability causing inflammation and oedema
Give two examples of type one hypersensitivity reactions
Asthma
Anaphylactic shock
What is the cause of type two hypersensitivity?
Antibodies (IgM or IgG) direct an immune response against self antigens or harmless extracellular antigens bound to self-cells. The immune response will trigger the complement cascade and apoptosis
Give three examples of type two hypersensitivity reactions
Autoimmune haemolytic anaemia
Neonatal isoerythrolysis
Blood transfusion reactions
What is the cause of type three hypersensitivity?
IgG antibodies bind to soluble antigens, forming free-floating antigen-antibody complexes. These free-floating complexes aren’t as immunogenic so aren’t engulfed as quickly by macrophages and end up being deposited and building up in the capillaries, stimulating the complement cascade and inflammation
What causes type four hypersensitivity?
Type four hypersensitivity is primarily mediated by T-lymphocytes binding to allergens, stimulating a delayed allergic response
What causes immunodeficiency?
A defect in any aspect of the immune system
