FOUND-SOM-immunity Flashcards
What are the functions of the immune system?
- protect host from pathogenic microbes
- can help protect against cancerous cells
- tissue homeostasis and tissue repair
which pathogenic microbes does the immune system protect against?
- bacteria
- viruses
- fungi
- parasites
what are the 3 main types of immunity?
- physical
- innate (non-specific)
- adaptive (specific)
what is an antigen?
a molecule (or fragment of a molecule) that is recognised by antigen receptors expressed by T and B cells of the adaptive immune system, stimulating an immune response
what is an epitope?
part of an antigen recognised and bound by an antibody or by antigen receptors on T and B cells
What are the differences between innate and adaptive immunity (6)?
INNATE
-constitutive-always on
-responds rapidly
-relatively non-specific
-no memory response
-does not get more effective upon second exposure
-keeps infection under control until adaptive immunity kicks in
ADAPTIVE
-requires priming by antigens
-responds slowly (days)
-highly specific
-memory response
-self/non-self discrimination-avoids auto immune disease
-becomes more effective with repeated exposures
what are different cells associated with the innate immune system (7)?
- macrophage
- dendritic cells
- natural killer cells
- mast cells
- neutrophils
- basophils
- eosinophil
what are examples of sentinel cells and what is their role?
macrophage/ dendritic
- reside in tissues and recognise invading pathogens
- process information about the immune status of surrounding tissue and may consequently transmit these signals to the peripheral nervous system via production of cytokines
what is the role of phagocytes?
- reside in tissues or recruited from blood-engulf and kill invading pathogens by phagocytosis
- present pathogen’s antigens on cell surface-alert adaptive immune system
what are the roles of innate lymphoid cells?
- reside in tissues or recruited from blood
- NK cells kill infected or transformed cells
- produce cytokines
what are cytokines?
-broad category of small proteins that can be released from cells to carry out a variety of functions
Which cells are involved in the adaptive immune response?
- CD4+ T cells-helper
- CD8+ T cells-killer (cytotoxic T cells)
- B cells
where do CD4+/ CD8+ T cells develop?
-thymus
where do B cells develop?
-bone marrow
what are the roles of CD4+ T cell?
- secrete cytokines and chemokines
- cytokines communicate with other immune cells and activate other effector cells
- help B cells for antibody production
- help macrophage activation
- help neutrophil activation
- T reg cells suppress activity of other immune cells
what are the 2 main jobs of senitinel immune cells?
- destroy pathogen-phagocytosis
- initiate inflammatory response
what are the cardinal signs of inflammation?
- heat
- redness
- swelling
- pain
- loss of function
How do sentinel cells initiate an inflammatory response?
sentinels—->release of vasoactive molecules-cause vessels to leak and dilate-more WBCs to area
—>cytokines, chemokines-recruiting other immune cells (neutrophils, monocytes)——>increase vascular permeability—>inflammation
—>production of acute phase proteins-activate complement cascade from blood to tissue——>inflammation
how do dendritic cells alert the adaptive immune system?
- recognise, engulf and degrade pathogens-phagocytosis
- degrade protein antigens into short peptides
- take peptides and display on cell surface
- leave infection site and travel through lymphatic vessels to nearest draining lymph node-present those antigens to T cells
what is another name for dendritic cells?
Antigen-presenting cells
what are the roles of antibodies?
- bind and neutralise pathogens and enhance their uptake by phagocytes
- can activate complement to kill pathogens
what is the structure of antibodies?
-2 heavy pp chains
-2 light pp chains
-2 identical binding sites
-variable region-complementary to specific antigen
(FAB region)
-C-termini of 2 heavy chains combine to form Fc region-complement activation/ interaction with other immune cells
which cell type is most involved in cutaneous immunosurveillance?
Langerhans cell
what is a reticulocyte?
an immature erythrocyte without a nucleus
-formed in bone marrow and sent into circulation after about 2 days
what is the appearance of macrophages?
central round nucleus with a vacuole
what is the appearance of dendritic cells?
large branchlike projections coming off the body
what is the appearance of natural killer cells?
- single-lobed nucleus
- very little cytoplasm
what is the appearance of mast cells?
- ‘fried egg’ appearance of nucleus and cytoplasm
- granules
what is the appearance of neutrophils?
- multilobed nucleus
- granules
what is the appearance of basophils?
- 2-lobed nucleus
- purple-staining
- granules
what is the appearance of eosinophils?
- 2-lobed nucleus
- orange-staining
- granules
what does a monocyte develop into?
macrophage
what are the roles of macrophages?
- phagocytose pathogens
- may present the digested antibodies to stimulate the rest of the immune system
what are the roles of dendritic cells?
- phagocytose pathogens
- presents digested antibodies to trigger adaptive immune response
what is the role of natural killer cells?
-kills tumour and virus infected cells by releasing perforin
what are the roles of mast cells?
- causes vasodilation and inflammation
- degranulation to release heparin and histamines
- can phagocytose and present antigens too
what are the roles of neutrophils?
first responder at the site of infection
- degranulates releasing toxins which kill pathogens
- can also phagocytose
what are the roles of basophils?
- defends against parasites
- causes allergic inflammation by degranulation to release histamine and heparin
what are the roles of eosinophils?
- defends against parasites
- causes allergic inflammation by degranulation to release histamine and heparin
what are the 3 types of innate immunity cells?
- granulocyte
- sentinel/phagocyte/APCs
- lymphocytes
what are the roles of granulocytes in the innate immune system?
-kill pathogens by degranulation-releasing lots of inflammatory molecules/ cytokines
what are the roles of sentinels/ phagocytes/ APCs in the innate immune system?
- Cells which detect pathogens, then engulfs them and presents the remnants on their own cell surface to alert the rest of the immune system
- Tissue resident
- Monocyte forms either macrophage or dendritic cells (main APCs)
what are the roles of lymphocytes in the innate immune system?
- Tissue resident or recruited from the blood
- Kills infected cells
- Produce cytokines
what is the nature of the physical immune system?
constitutive (always on)
what are the cellular mediators of the physical immune system?
-epithelial cells eg respiratory tract/ GI tract/ skin-dermis
what are the extracellular mediators of the innate immune system?
- cytokines
- —>small proteins-that can be released from cells to carry out variety of functions
- acute phase proteins
- –>Proteins which are released in response to inflammation or some which are involved in the complement cascade, or blood clotting
- complement
- —>Proteins which are released at the end of the complement cascade to cause cell death
what are PAMPs?
Pathogen-associated molecular patterns
-protein/ structures on the surface of pathogens which are not commonly found on the host tissue
what are DAMPs?
damage-associated molecular patterns (DAMPs)
-molecules released from dying host tissue
what are PRRs?
- pattern-recognition receptors
- receptors on top of sentinel cells (macrophage/ dendritic) that detect PAMPs and DAMPs
which immune system are PAMPs/ DAMPs/ PRRs associated with?
innate
describe the process of pathogen detection using PAMPs/ DAMPs/ PRRs?
- Macrophages or dendritic cells will use their PRRs (e.g. TLRs) to bind to DAMPs to recognise that host tissue is being damaged.
- Chemotaxis will draw immune cells to the area.
- They will also use their PRRs to bind to PAMPs on the pathogens to detect them as foreign material, before phagocytosing them.
what are the ways in which WBCs can kill pathogens once detected by PAMPs and DAMPs?
- phagocytosis
- degranulation
- NETosis-neutrophil extracellular traps
Describe how NETosis kills pathogens.
neutrophils can release their chromatin in a web of fibres to trap the pathogen and kill it
describe how degranulation kills pathogens.
releases granules which kill the pathogen-usually by creating holes in their cell membrane-so they leak out
describe the ways in which the complement cascade can be activated.
- LECTIN via carb-binding mediators-Mannose binding lectin (MBL) binds to Mannose on pathogens surface-cascade-activating C3 convertase
- CLASSICAL-using IgG antibodies-recognise pathogens by binding to antigens on pathogen’s surface-creates C1 complex-cascade-activate C3 convertase
- ALTERNATIVE-direct contact with pathogens -complement proteins factors B, D, P interact directly with pathogen-C3 convertase activated
outline the two paths of the complement cascade
1) C3 convertase–>C3—->C3a + C5a—–>Binds to mast cells which release histamines-increases vascular permeability and attracts phagocytes
2) C3 convertase—->C3a +C3b—–>C5—->C5a +C5b—–>C6 +C7—>C8+C9—–>Membrane attack complex (MAC) form a cylinder which inserts into the pathogens cell membrane-the pathogens contents leak out and it dies
what is the lymphatic system?
network of lymph nodes that spread throughout the body
what are the functions of the lymphatic system?
- drains excess interstitial fluid from tissue spaces into the blood
- transports dietry lipids-vitamins A/D/E/K absorbed by the GI tract
- carries out immune response
what are primary lymphoid organs?
- red bone marrow and the thymus-where lymphocytes are formed and mature
- T-cells and B-cells are born here but T mature in thymus
what are secondary lymphoid organs?
include: lymph nodes
- tonsils
- spleen
- peyer’s patches (ileum)
- secondary mucosa associated lymphoid tissue (MALT)
what are Peyer’s patches?
-small clusters of lymph nodes in the ileum that monitor for bacteria and are important in preventing pathogenic bacteria culturing in intestine
what are the two types of tissue in the spleen and what do they do?
-white pulp-lymph tissue consisting of lymphocytes and macrophages arranged around central arteries-similar to lymph nodes functionally
- red pulp-consists of venous sinuses and splenic or Billroth’s cords-consists of RBCs/ macrophages/ lymphocytes/ plasma cells/ granulocytes
- removes defective platelets and RBCs/ stores platelets/ produces blood cells during foetal life
what are the 2 lymphatic ducts and what parts of the body do they drain?
- right lymphatic duct
- thoracic duct
- upper right quadrant drains into right lymphatic duct
- everything else drains into thoracic duct
what do immunoglobulins do?
- neutralise pathogens and pathogen products before they cause too much damage and before WBCs digest them whilst they’re still harmful
- also activate other parts of immune system
- activate complement pathway
- opsonisation-help WBCs phagocytose pathogens
- neutralisation-bind toxic pathogenic products
- agglutination-group pathogens together-easier to phagocytose
what are the 5 classes of antibodies?
- IgM
- IgG
- IgA
- IgE
- IgD
What is the structure of IgM?
- largest in size
- pentameric structure-allows it to bunch lots of pathogens together for phagocytosis
what are the functions of IgM?
- —->aggutination
- neutralistaion
- opsonistaion
- predominant antibody in primary antibody response
- first antibody detected in blood after infection
what is the structure of the IgG?
- same basic structure
- variable Fab region which will bind to pathogen
- constant Fc region which will bind to WBCs for opsonisation
what are the functions of IgG?
- —->opsonisation
- neutralisation
- agglutination
- largest number-75%
- predominant antibody in secondary antibody response
- only antibody that can pass through placenta
what are the functions of IgA?
- neutralisation
- —>blocking
- predominantly antibody found in mucous/ secretion/ breast milk/ mucous (respiratory and GI tract)
where are IgA produced?
epithelial cells
what is the function of of IgE?
- —>parasite defence
- —->allergic response-by binding to and activating mast cells
- low quantity
where is IgD found?
on the surface of B-cells as the receptor of antigens
what is the role of IgD?
- —->B-cell receptor-antigen bind to IgD antibody-activate B cell
- allows the adaptive immune response to progress
what is the humoral response?
- This is the process by where B-Cells are made aware of pathogens circulating in the blood/lymph.
- The B-Cells can then differentiate into plasma cells, to produce antibodies.
describe the steps of the humoral immune response.
1-Mature B-Cells are produced in the bone marrow, and then circulate in the blood and lymph.
2-The B-Cell will become activated when the antigen binds to its B-Cell Receptor (IgD antibody). This forms a complex.
3-The complex is internalized by the cell and broken down into fragments – one part of the pathogen fragment is combined with an MHC Class II Molecule to form a new complex. This is inserted onto the B-Cell surface
4-A CD4+ Helper T-Cell will bind and recognize this complex on the B-Cell. The CD4+ Cell will release IL-2 to activate that B-Cell, and make it proliferate into plasma cells
5-The plasma cells will make and secrete antibodies which can bind the antigen which was in the complex.
6-Memory B Cells are also produced by the activation
what are MCH class molecules?
proteins of cell surfaces that present antigens to T-cells
what is the difference between MHC Class I and MHC Class II?
- MHC Class I-found on surface of every nucleated cell
- present antigens to CD8+ T-cells
- MHC Class II-found only on surface of APCs
- present antigens to CD4+ cells
what are the genes for MHC molecules?
- genes for MHC Molecules are on Chromosome 6 and they are called Human Leukocyte Antigen (HLA) genes
- large variety of genes means MHC molecules can present lots of different antigens
how are MHC molecules polygenic?
here are multiple genes which are required to code MHC Class I (3), and MHC Class II (6) molecules. Since you get one from each parent, you will have 6 MHC Class I Molecules, and 12 MHC Class II Molecules on each cell.
how are MHC molecules polymorphic?
Each gene has multiple alleles; resulting in a huge number of potential combinations
what is positive selection?
Immature T-Cells that bind well with MHC Class I molecules will become CD8+ Cells.
Immature T-Cells that bind well with MHC Class II molecules will become CD4+ Cells.
what is negative selection?
immature T-Cells that bind well with any other self material will undergo apoptosis.
This is called central tolerance and will prevent immune reactions against your own body tissue.
This process goes wrong in autoimmune diseases.
outline the general steps of the humoral response?
1-use of specific, polygenic/ polymorphic MHC molecules
2-T cell -selection and proliferation in the thymus
3-Antibody response
what occurs in the primary antibody response?
Slow and small amount of antibody produced need to activate B-Cells
The predominant antibody in this response is IgM
what occurs in the secondary antibody response?
Rapid and large amounts of antibody produced
memory B-Cells already made
The predominant antibody is this response is IgG
do antibodies kill pathogens directly?
no they help other immune cells to kill pathogens
what are the features of exogenous antigen processing?
- Pathogens from outside the APC (e.g. bacteria) are internalized by phagocytosis.
- Proteases (cathepsins) break down the bacteria in one lysosome package
- The ER synthesizes its own MHC Class II Molecule in another lysosome package
- The two lysosome packages fuse
- The package is exocytosed so that the MHC-Pathogen complex is presented on the surface of the cell, where CD4+ cells will bind to the complex
-does not kill pathogens directly-the APC alerts other immune cells which will kill the pathogens (positive feedback loop)
what are the features of endogenous antigen processing?
- Pathogens inside nucleated cells (i.e. viruses) are already inside the cell (no need to phagocytose)
- Proteases (cathepsins) break down the virus in the cytoplasm into fragments
- The ER synthesizes its own MHC Class I Molecule in a lysosome package
- The fragments are transported to the ER where it fuses with the MHC Class I Molecule in the package
- The package is exocytosed so that the MHC-Pathogen complex is presented on the surface of the cell, where CD8+ cells will bind to the complex
- Kills pathogens directly –>CD8+ cells will release perforin and granzymes which will perforate the cell membrane of the pathogen, killing it
what are the 5 different types of T helper cells?
Treg Th1 Th2 Th17 TFH
what is the role of Treg?
immune regulation
what are the 2 roles of Th2?
- promotion of IgE
- activation of eosinophils
what are the 2 roles of Th1?
- promote macrophage activation–>phagocytosis
- cytotoxic T cell proliferation
what is the role of Th17?
-neutrophil activation
What is the role of TFH?
B cell production of antibodies
