Immunity- state of resistance to foreign material that is characterized by specificity and memory.

Two types of immunity
1) cell-mediated immunity - this is immunity mediated by T-cells. T cells secrete lymphokines (e.g. interleukin-2) which then go and interact with other cell types, and either activate or repress an immune response.
2) humoral immunity - this is blood-specific immunity mediated by antibodies

Each different response is mediated by different sets of lymphocytes. Following an insult, lymphocytes proliferate (i.e. divide) and differentiate (i.e specialize). There are two catergories of lymphocytes:
a) B lymphocytes - these are found fixed in the lymph nodes, liver and spleen. They are a bone marrow-derived lymphocytes, that mature in PeyerÕs Patches of the pancreas. During maturation, antigen-specified antibody is displayed on the cell surface. If activated by antigen, the B cells excrete antibody.
b) T lymphocytes - these are also found in the lymph nodes, liver and spleen, but some are also found freely circulating in the blood. This is a lymphocyte that matures in the thymus. They have cell surface receptor of pre-determined specificity. The main job of these cells is to regulate cellular immunity. There are two main types: helper T cells (CD4+) and suppressor/cytotoxic (CD8+).

A third important cell type are macrophages. These cells play an essential role in processing and delivering immunogens to the lymphocytes (called the afferent branch) as well as being important effector cells (i.e they carry out destruction of foreign material). They also carry receptors for antibody molecules which allows them to reach out and grab foreign stuff, prior to destroying it.

Two types of acquired immunity:
1) Active immunity - here a specific immune response is mounted by the host in response to an infection.
2) Passive immunity - this is the transfer of preformed antibodies to a non-immune individual via blood, serum components etc. This is how babies achieve a certain degree of immunity at very early ages (i.e. the mother transfers some of her antibodies to the child through the fetal blood supply as well as by breast feeding (Abs are found in the milk). Passive immunity can also be acquired through the injection of Abs. This is how a toxin is negated (e.g. snake venom, tetanus).

In order for an immune response to be activated, an object must first be recognised as foreign. An immunogen is any molecule that stimulates an immune response. In general, proteins are the best immunogens, followed by carbohydrates and then nucleic acids. Lipids are very poor. An antigen is any molecule that reacts with an immune response. Often, antigen and immunogen are the same thing.

There are two branches of the immune response:
1. Afferent branch: this is all those reactions that lead up to an immune response. This includes the chewing up and presentation of antigens by the macrophages. When they do this, specific B and T cells are stimulated, they begin to diviide and produce either lymphokines or antibodies. This takes about 4-7 days. Once completed, the immnue system is said to be sensitized.
2. Efferent branch: thse are all the reactions which result from the immune response.

Kinetics of an immune response (see Figure 19:1)
Upon an initial infection, it takes about 4-7 days for the immune response to be manifest. After seven days we get what is known as the primary immune response. Here IgM is initially produced but the B cells differentiate further into IgG producing cells. After about three weeks the primary immune response is turned off. However, during this initial period not only are Ab producing cells are made but also memory B cells are also formed. Consequently, when the same agent is encountered by the host again, the body recognises that its seen this before, and stimulates the memory cells to pump out Abs. This is called the secondary response. Memory can last for a few weeks or alternatively can last for years.

So what happens when a pathogen enters your body? Basically, antibodies are made to all the various components of the bacterium e.g. pili, flagella, LPS etc (see Figure 19:2). Abs recognize antigenic determinants or epitopes. Epitopes can be as small as 4-5 amino acids There are three types of effector immune response.
a) humoral (blood) - this is antibody response mediated by B cells and regulated by T cells.
b) cell-mediated (cellular) - this is delayed-type hypersensitivity and cytotoxicity mediated by CD4+ and CD8+ T cells.
c) tolerance - this is a non-specific response mediated by T cells. Naturally we are tolerant to out own tissues (sometimes it gets out of whack and the indiviual has severe consequences to deal with).

Antibodies
These are large glycoproteins which are released by B cells (see Figure 19:3). Antibodies (Abs) specifically interact with antigens. There are literally millions of antigen specificities that the body can produce, and this is done genetically as the B cells mature.

There are five classes of Ab:
IgM - this is the largest Ab and the first one to be made in an antibody response. These Abs are able to mediate neutraliztion, fix complement, agglutinate and immoblize antigens (see Figure 19:4).
IgG - this is the main serum Ab. This is synthesized during the secondary immune response. Able to do all Ab mediated functions.
IgA - this is mucosal antibody. Sometimes called secretory Ab as mucosal cells secrete them when mucosal pathgens begin to establish colonies.
IgD - this is receptor antibody found on the surface of immunocompetent cells. This functions in the afferent response.
IgE - this is the reaginic Ab. Binds to the surface of mast cells and causes the degranulation (i.e. dumping) of histamine into circulation. Consequently, this ab is involvedwith allergies.

Abs are important for us in five ways (see Figures 19:5 and 19:6)
i) neutraliztion - here an Ab molecule covers up sites on a toxic molecule or virus.
ii) opsonization - this is Ab-mediated phagocytosis. This occurs with macrophages, which have antibody receptor sites on their surface. Consequently, they are able to grab hold of the anitgen, and then take it up to destroy it.
iii) complement fixation - this is a compicate system that reacts to antigen/antibody compexes. When antigen/antibody compexes stimulate the complement response, a cascade reaction is initiated, whichb attracts macrophages and allows substances to be released that dissolve membranes in foreign bodies.
iv) agglutination/precipitation - here Abs cross-link antigens into large complexes which make them easier to phagocytose and destroy.
v) immobilization - here Abs bind to flagella etc and prevent these organisms from escaping macrophage death.

Complement
This is a series of 11 serum proteins which are activated in cascade fashion. Complement can be activated either by: interaction with Abs

alternative pathway activated by lipopolysaccharide (LPS). Once activated, the response is amplified, is chemotaxic, results in immune adherence, and finally cell lysis.

Cellular Immunity (see Figure 19:7) Cellular immunity is often directed against intra cellular parasites (e.g viruses, tuberculosis etc) and cancer. Infected cells are killed by macrophages under the directions of CD4+ (helper cells) T cells. As well as macrophages interactions, cytotoxic T cells (CD8+ directed) also participate by releasing toxic components which kill the cell. A major problem for the cellular response is that they must be able to recognise self, especially as many of their targets are cells infected by agents that are within them. This means killing ones own cells in an effort to rid the infection. Self recognition is mediated by histocompatibility antigens (MHC antigens). All our cells display these MHC antigens in specific patterns on the cell surface.

For the cellular response to succeed, macrophages must first process the antigen and then display pieces of the antigen on its cell surface. They then present this antigen to the T cells, which then recognize the antigen as being foreign as well as recognising the MHC antigens. If the T cell sees both antigen and MHC is becomes activated: if it sees only the MHC antigen nothing happens. When macrophages display antigen plus either Class I MHC they stimulate CD8+ cells (i.e. they make cytotoxic T cells); or antigen plusClass II MHC they stimulate CD4+ cells (i.e. helper T cells). It is the depletion CD4+ cell type that causes AIDS infected patients to become prone to secondary bacterial infections.

Immunization (see Figures 19:8 and 19:9) This works because of the memory cells made in the immune system. Basically what happens is that as well as producing Abs, the B cell clones also maturate into memory cells. So if an antigen is seen again by the body, the memory cell is triggered and you get clonal expansion of that specific clone. Consequently, clonal expansion produces many cells producing specific Ab.

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