T cell mediated immunity is there to: Detect and eliminate pathogens that live

and eliminate altered cells e.g. tumours

Intracellular pathogens require a different strategy to extracellular pathogens. You can't just have a humoral response, you need a

response and this is done by T-cells. Naive T-cells are activated in the secondary lymphoid organs e.g spleen, lymph nodes etc

Lymphocytes recirculate in the blood and lymph nodes via post capillary vessels called

(HEV). Recirculation increases likelihood to encounter an antigen, only effector cells can enter non-lymphoid tissue, which means that

lymphocytes can't. They migrate via diapedesis. The T-cell needs an antigen in order to become an

They also require co-stimulation and are silenced without it. Antigen recognition without co-stimulation leads to tolerance, the T-cell becomes

Activated T-cells can secrete and respond to interleukin typev

(autocrine stimulation). Activation of naive T-cells causes the expression of high affinity IL-2 receptors. IL-2 binds to this and promotes T-cell growth and proliferation

In essence, on recognition of the antigen, the T-cell starts specific proliferation and differentiation and can go on to fulfil its

function. IL-2 also activates T-helper cells, types 1 and 2. These secrete more IL-2 and activate

T-cells.

Cytotoxic T-cells- Immature CD8+ cytotoxic T-cells that haven't encountered an antigen are called CTLp (Cytotoxic T-lymphocyte precursors). These are stimulated to mature by

and the antigen they present, which leads to the production of an antigen activated precursor cytotoxic T-cell. It needs to be

This Ag-activated CTLp expresses an IL-2 receptor. As said previously, the IL-2 secreted by T-helper cells activated the Ag-activated CTLp to mature and form a mature CTL. They can then

and undertake their effector function. Specific recognition of target cells by the CTL causes

This allows granules to be released at the site of cell contact. The release of granules by the CTL results in the death of the target cell via

The proteins used are Perforin which forms

that allow granzymes and granulysin in, Granzymes are serine

and Granulising induces apoptosis. Also the CTL can mediated cell death by using Fas-FasL interactions: Interaction between the Fas protein on the target cell and the Fas ligand on the CTL causing a cascade of enzymes to initiate apoptosis

CD4+ cells are critical in host defence. Naive CD4+ cells can differentiate into distinct subsets after encountering

These subsets produce restricted cytokine patterns. T-helper cell type 1 are responsible for activating

via IFN-gamma (cytokine) which is also responsible for activation of B-cells. T-helper cells type 2 are responsible for

responses and parasitic infection responses, they activate

and B-cells which stimulate mast cell degranulation

Regulatory T-cells - these control the immune response by cell contact and cytokines, this maintains immunological tolerance and prevents

They are necessary to maintain tolerance to self-antigens

The immune system not only recognises and responds to antigens, it can also

subsequent encounters with the same antigen. Memory responses are characterised by a faster and stronger immune response that eliminates pathogens quickly and prevents disease. This is the basis of

It is the most important consequence of the acquired immune response. In contrast to B-cells, T-cells

undergo isotype switching or affinity maturation. Memory T-cells express CD45RA, which allows us to differentiate them from naive T-cells. They also express CCR7 which is a

receptor that controls homing to secondary lymphoid organs.

Primary lymphoid organs are where lymphocytes are

These are the bone marrow and

Secondary lymphoid organs are where lymphocytes can interact with

and other lymphocytes. These are the spleen, lymph nodes and

(MALT)

Human thymic lobe- The thymus is deep in the

It has nodules, the thymus is very densely packed with lymphocytes in the

and it's less densely packed in the

During infection, there is

change in the structure of the thymus. Bone marrow is the site of

Bones have holes to allow sinuses and blood vessels through. During infection, feedback to the bone marrow causes stimulation of

The lymphatic system is used to drain

back to the circulation. They drain through lymph nodes to go back to the circulation via the

This means that antigens from an infection pass into the local lymph node. Lymph enters via the

and exits via the efferent lymphatic system. B-cells are stored on the outside of the lymph node, in lymphoid

T-cells are stored separately towards the middle of the lymph node.

centres are masses of rapidly proliferating B-cells during an immune response. During an infection, they're seen and these are a sign of distinction between the infected and healthy state. To get from the blood to the lymph, a specialised cell. the high endothelial

allows the T and B-cells to leave the circulation to migrate to their positions into the node. Characterised by

The spleen is a filter for

in the blood. The blood supply is via the

vessels. There are two parts, red pulp and white pulp. Red pulp is associated with

turnover. White pulp is where the immune stuff happens, it's adjacent to vessels and lymphocytes.

The area immediately near the arterioles is called the

This is the T-cell area, the presence of germinal centres is seen in infection in the spleen

are the first line of defence against disease. The mucosa and

form a physical barrier. It has a very large surface area. It is heavily defended by the immune system, MALT and cutaneous immune system. One example of MALT is seen in the gut. The gut has a lot of lymphatic coverage, there are areas of lymphoid tissue called

They have aggregates of lymphocytes. Above these are M cells, which sample the contents of the guts for antigens. They uptake any antigens and give them to

in Peyer's patch

The cutaneous immune system- Keratinocytes act as a

There are lymphocytes in the epidermis, Langerhans cells are also there, serving a similar function to M cells in the gut. All the previous cells are in the

The lymphatic system underneath the epidermal layer is there to provide drainage and immune coverage. Antigens can go to the lymph nodes for presentation to the lymphocytes

There is a problem: There are very large numbers of B and T-cells with different specificities but there may be limited amounts of

The body needs to ensure that the antigen meet its lymphocyte. This happens via anatomical structure of immune system and lymphocyte

Naive lymphocytes are put into the blood and they circulate in the blood and peripheral lymphoid tissue until they

or encounter the antigen in which case they become

In order to move cells from the blood into the lymph nodes they must extravasate:

Rolling- As cells move across the blood stream, a specialised molecule called

is used as a cell-cell adhesion factor, which binds the endothelium to the cell. It can be expressed on the endothelium surface or on the extravasated cell's surface

Activation-

attract the cell closer to the endothelium of the vessel. It causes integrins to be activated on the surface of the endothelium. Integrins change

Adhesion- Integrins are changed from a low affinity conformation to a high affinity conformation and bind to molecules on the endothelium and remain

on this part, despite blood flow. They then migrate into the tissue, in this example, the lymph node via transendothelial migration

The described process is called

and is how all immune cells move from the circulation into other tissues

Under the microscope, B and T lymphocytes

be told apart. We can identify them using

as different lymphocytes express different cell surface receptors. Thus different types are classified by recognition of sites by antibodies. The antibody sticks to the specific cell surface protein it targets. The antibodies

around the cell which expresses their protein. These clusters are used to differentiate between different cell types.

T-lymphocytes- All express

There are two types of T-cell receptor - alpha beta and gamma delta. Two thirds of alpha beta express

and the other third express CD8. CD4+ T cells= T helper cells, regulatory cells that secrete

CD8+ T cells -

T cells (lyse infected cells and secrete cytokines). Thymic output

as age increases. T-cells only recognise processed antigens at the surface of another cell using their TCR

B-lymphocytes- Have an immunoglobulin molecule as their BCR. They express CD19 and

They also express MHC class II, they produce

B cells recognise intact antigens free in body fluid

Antigen presenting cells - cells that present processed antigens to

to initiate the acquired immune response. Dendritic cells are a bridge between innate and acquired immune system, widely spread e.g. in skin and

B-lymphocytes and activated macrophages. All of these present to T-cells

Pathogen-associated molecular

(PAMPs) are specific types of molecular structures found in cells such as double stranded

, certain carbohydrates. They're detected by receptors on the surface of cells or in the

There are

receptors TLRs (cell surface and intracellular) and RIG-I like receptors

Different cell types use different receptors to detect, the receptor upon activation elicits a signalling

resulting in anti-viral responses, releasing molecules such as

which is an enzyme that degrades viral nucleic acids and retroviral restriction factors.

This is an

response to tissue damage. Results in fever and followed by the increased production of proteins mainly by the

These are acute phase proteins: C-reactive protein binds to molecules found on the

of some bacteria and fungi. Serum amyloid protein - same as above and Mannan-binding

which binds to mannose sugar molecules which are not often found on mammalian cells. These molecules direct

to identify and ingest the infectious agent.

Innate immunity is present from birth and isn't antigen specific but it can recognise pathogen associated

(PAMPs) using a small number of receptors to recognise molecular patterns specific to pathogens. It does not have memory but uses cellular and humeral components. It's rapid and cooperates and directs the adaptive immune response by using danger signals.

Phagocytes are the main cells of the innate immune system, the use phagocytosis which is a process of taking up pathogens and then

them. There are multiple processes: Engulfment by

, phagosome formation, fusion with lysosome to form phagolysosome, killing/digestion then waste release

Two main types of phagocytic cells in the innate immune response: neutrophils and

Neutrophils are 50-70% of leukocytes, they're short-lived, circulate in the blood then migrate via diapedesis into tissues, they're the first cells to be recruited into a site of damage. They contain granules containing

such as peroxidase, lysozyme and other hydrolytic enzymes

Macrophages are less abundant, they're dispersed throughout tissues, they signal infection by releasing soluble

When many neutrophils are involved in fighting infection, the formation of

is seen. Phagocytosis is much more effective after antibodies opsonise a target pathogen because opsonisation

the pathogen with proteins to facilitate phagocytosis. They bind to the antigen and phagocytes bind to them. Neutrophils have multiple killing mechanisms, they're either

dependent or independent. The dependent ones use a respiratory burst which uses toxic metabolites and reactive nitrogen intermediates. The independent ones use enzymes and microbial peptides

Monocytes circulate in the

when they migrate into tissues they become

They have pattern recognition receptors to recognise PAMPs. They express receptors for many bacterial constituents.