Anatomy of the immune system Flashcards
What is the bodys first line of defence
physical, chemical, and mechanical barriers such as skin, tears, mucus and stomach acid
if pathogens evade the bodys first lines of defence they encounter what part of the immune system
the inante
how does the innate system recognise pathogens
the innate immune system evolved the ability to recognise structural elements such as specific glycolipids or forms of nucleic acids that are well conserved in pathogens but absent in the host organism. the innate immune system uses a family of receptors known as toll-like receptors (TLRs) to recognise these specific molecular characteristics in most pathogens, often called a pathogen-associated molecular pattern (PAMPs).
what cells are part of the innate immune system
phagocytes, eosinophils, basophils, mast cells and natural killer cells.
whata re the two components of the adpative immune response
humoral and cellular component
how does the body recognise intracellular pathogens
Because intracellular pathogens do not leave markings vertebrates have evolved a mechanism to mark the exterior of cells with a sample of the interior contents, both self and foreign. These peptides are displayed by integral membrane proteins that are encoded by the major histocompatibility complex (MHC). T cells continuously scan the bound peptides to find and kill cells that display foreign antigen motifs on their surface.
what is the function of Th cells
contributes to both the humoral and cellular immune responses by stimulating the differentiation and proliferation of appropriate B and cytotoxic T cells.
what are the primary lymphoid tissues
thymus and bone marrow
Leukocytes are divided into 6 groups what are these
Leukocytes are divided into 6 basic types: (1) basophils in the blood and mast cells in the tissues; (2) eosinophils; (3) neutrophils; (4) monocytes and their derivative macrophages; (5) dendritic cells; and (6) lymphocytes.
what is the MOA of basophils (mast cells) and what type of infection/pathology are they implicated in
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Basophils and mast cells (granulocyte):
They contain large cytoplasmic granules with inflammatory mediators, namely histamine. Histamine is responsible for some of the symptoms of an allergic reaction: runny nose, itching, watery eyes etc. The function of basophils has never been proven, but they are often found in parasitic infections. Basophils are related to mast cells of tissues.
what is the MOA of eosinophils and what type of infection/pathology are they implicated in
Eosinophils (granulocyte):
Play a role in the bodies defence against parasitic invaders: eosinophils attach to large antibody-coated parasites and release substances from their granules that damage or kill the parasites. Granules of eosinophils contain many enzymes such as peroxidase, RNase, DNase, lipase, plasminogen and major basic protein. All mediators released by eosinophils are toxic to both parasites and host tissue. Eosinophils also participate in asthma and allergic reactions, where they contribute to inflammation and tissue damage by releasing toxic enzymes and oxidative substances.
what is the MOA of neutrophils and what type of infection/pathology are they implicated in
Neutrophils are phagocytic cells that typically ingest and kill 5-20 bacteria during their short, programmed life span of two to three days. In addition to ingesting bacteria and foreign particles, neutrophils release a variety of cytokines and chemical mediators of the inflammatory response.
what is the MOA of macrophages
Monocytes are the precursor cells of tissue macrophages. Macrophages are the primary phagocytic scavengers within tissues. They are larger and more effective than neutrophils, ingesting up to 100 bacteria during their life span, which is why they get their name “big eaters”. Macrophages also remove larger particles, such as old red blood cells and dead neutrophils. Macrophage is the general name, but they are named differently depending on what tissue they are found in e.g. osteoclast is the macrophage found in bone, Kupffer cells in the live etc.
what is the MOA of dendritic cells
dendritic cells are macrophage relatives characterised by long, thin processes that resemble dendrites of neurons. Dendritic cells are found in the skin (where they are called Langerhans cells) and in various organs. The play a key role in linking innate and adaptive immune responses by displaying bits of foreign antigens that have been ingested and processed.
what is the MOA of NK cells
- Natural killer (NK) cells: are an important part of the innate immune response against viral infections. Unlike phagocytes they don’t engulf the microbe to kill them instead they bind the pathogen and release two different components: perforins (puts holes in the cells) or granzymes
the complement cascaade is a major player in the innate immune response. What are the 3 ways of activating this
- Foreign antigen identified by antibody (classical pathway)
- Carbohydrates on microbes (alternative pathway)
- Circulating lectin (lectin pathway)
what does all the different pathways of the complement cascade ultimately result in
proteolysis of complement protein C3 resulting in the formation of the membrane attack complex
what does the membrane attack complex do
puts holes in pathogen
The inflammatory response has four classic signs:
redness (rubor), heat (calor), swelling (tumor) and pain (dolor).
where does haematopoiesis take place
bone marrow
A CD4 T cell is a
helper t cell
a CD8 t cell is
cytotoxic t cell
what type of MHC receptors do CD4 and CD8 T cells recognise
MHC II and I respectively
what is the process of positive and negative selective for TCR
positive = selected if interact with appropriate THC
negative = killed if recognise self
how do cytotoxic T cells kill pathogens
they bind to MHC-I receptor displaying pathogen they then release a cytotoxic pore-forming molecule called perforin along with granzymes, enzymes related to digestive enzymes trypsin and chymotrypsin.
how do Th cells participate in the adaptive immune response
they bind to the MHC -II receptor on APC. this binding stimulates the release of cytokines which stimulates the growth and differentiation of different immune cells.
List the different Thelper cells, their defining cytokine, target cells
discuss the structure of antibodies
Antibodies can be cleaved into three fragments of similar weighting: two of these fragments bind antigen and are called Fab (F stands for fragment, ab for antigen binding); the other fragment cannot bind antigen and is called Fc because it crystallises readily. Antibodies consist of two light (L) and heavy (H) chains both with variable and constant regions. The antibody binding region is Fab and the Fc region is involved in effector function via Fc receptors on other cells e.g. NK cells.
what are the different classes of antibody and what is their role
There are 5 different class of antibody: G, A, M, E and D.
IgG, is the antibody present highest in concentration in the serum and it functions as an opsonizer.
IgM is the first class of antibody to appear in the serum after exposure to an antigen. The presence of 10 antigen binding sites enables IgM to bind especially tightly to antigens containing multiple identical epitopes.
IgA is the major class of antibody in external secretions, such as saliva, tears, bronchial mucus and intestinal mucus. Thus, IgA serves as a first line of defence against bacterial and viral antigens.
The role of IgD is not yet known.
IgE is important in conferring protection against parasites, but IgE also participates in allergic reactions and anaphylactic shock.
describe the pathophysiology of IgE and allergy/anaphylaxis
On first exposure to an allergen (e.g. bee venom) some people, for reasons that are not fully understood, make lots of IgE antibodies against the allergen. Mast cells have receptors on their surfaces which can bind to the Fc region (the constant end) of the IgE antibodies. When these receptors are bound the Mast Cell is like a little bomb waiting to go off. On second exposure to the allergen the IgE antibodies which are bound to the mast cell triggers a cascade that leads to the release of granules containing pharmacologically active molecules. Histamine, one of the agents released, induces smooth muscle contraction and stimulates the secretion of mucus.
describe the process of a B cell switching to a plasma cell
Each (immature) B cell has a IgM antibody attached. Binding of a pathogen to its unique epitope (variable region) initiates oligomerisation or clustering of the antibody molecules.
This oligomerisation or clustering initiates an intracellular signalling cascade that activates gene expression, leading to the stimulation of cell growth, clonal expansion and initiating further B cell differentiation into plasma cells.
Intially these cells switch from membrane linked IgM to secreting IgM before then undergoing isotype switching to either IgG/IgA/IgE/IgD. In this switch, the light chain and the variable region of the heavy chain are unchanged. Only the constant region of the heavy chain changes.
After the pathogen has been successfully repulsed most of the short lived plasma cells die off. However, a few long lived plasma cells remain in the bone marrow, secreting low levels of antibodies to provide continued immunity. Some of the activated B cells become memory B cells that also stay alive, waiting for the next exposure to the same antigen.
define active and passive immunity
Adaptive immunity due to antibodies can be subdivided into passive and active immunity.
Active immunity occurs when the body is exposed to a pathogen and produces its own antibodies and memory cells. This can occur naturally, when a pathogen invades the body, or artificially, as when we are given vaccinations.
Passive immunity occurs when we acquire antibodies made by another organism. The transfer of antibodies from mother to fetus across the placenta is one example and is known as natural passive. Artificial passive immunity describes the process transferring lymphocytes from an immunised individual via injections.
Unlike active immunity, passive immunity provides an instant response, but its immunity is only temporary as memory cells are not created. Hence, the difference between active and passive immunity is that active immunity does not form memory cells.
define self-tolerance
When lymphocytes encounter antigens, they may be activated, leading to immune response or inactivated leading to tolerance. Antigens that induce tolerance are called tolerogens and tolerance to self-antigens is called self-tolerance.
failure of self-tolerance causes
Failure of self-tolerance results in immune reactions against self (autologous) antigens and such reactions are called autoimmunity, and the diseases they cause are called autoimmune diseases
how is central tolerance achieved in B and T cells
B cells = those that react with self peptides in the bone marrow are negatively selected targeted for apoptosis)
T cells = those that recognise MHC-I receptors are positively selected and those that recognise MHC with self are negatively selected
Some B and T cells that recognise self may escape into the periphery. How is peripheral tolerance achieved
Anergy: the T cell recognise the antigen presented on the T cell but it requires another signal (co-stimulation) to initiate a reaction. Hence, the cell becomes anergic or non-responsive
Suppression: Self-reactive T cells may be actively suppressed by inhibitory populations of T cells that recognise the same antigen – so called regulatory T-cells.
overcoming peripheral tolerance is likely to occur when
inflammation or tissue damage is present. The increased activity of proteolytic enzymes in inflammatory sites can cause both intra- and extracellular proteins to be broken down, leading to high concentrations of peptides being presented to responsive T cells. These novel peptides are known as cryptic epitopes. The structures of self-peptides may also be altered by viruses, free radicals or ionising radiation, thus bypassing previously established tolerance.
