Additional information

Characteristics of B cell lineages

Naive B cells are mature B cells that have not yet been stimulated by an antigen.

All B cells will be CD19 and 45R+, both of them are involved in receptor signalling.

Comparisons between MHC classes

As RBCs are non-nucleated, they lack both MHC I and II.

Interferon gamma can induce the expression of MHC II on cells that normally do not express it such as intestinal epithelial cells and vascular smooth muscle cells (atherosclerosis)

Gamma Delta T cells: They form a small subset of T cells with gamma and delta chains forming the TCR. They are present mainly in mucosa and epithelial surfaces. In contrast to alpha beta T cells, gamma delta T cells are activated in an MHC independent fashion. They respond to lipid antigens, viral and tumor antigens and metabolites.

Classical antigen presenting cells include dendritic cells, B cells, macrophages and Langerhans cells (dendritic cell counterparts in the skin).

Comparison of various APCs

Adhesion molecules involved in T cell function

Macropinocytosis: The uptake of large amounts of extracellular fluid and membranes as a single vesicle. Employed by dendritic cells and macrophages for antigen processing.

Natural killer or NK cells:* NK cells are large granular lymphocytes that do not pass through the thymus. They do not have CD4 or 8 and do not have an antigen receptor. They recognize and kill virus infected cells and tumor cells without the requirement that the antigens be presented in association with MHC. Rather, NK cells target cells that fail to display MHC I on their surface, such as virus infected cells.

Th 17 cells: They are a subset of CD4 cells that are important for mucosal immunity in GIT. They produce IL 17 which attracts neutrophils to the site of bacterial infections. HIV kills Th 17 cells.

Haptens: They can bind an antibody but cannot, by themselves, induce an immune response. When haptens are bound to carrier protein , they become immunogenic and can elicit T cell and antibody responses.

Tingible body macrophages: B cells undergo intense proliferation and somatic hypermutation in the germinal centers. B cells that accumulate deleterious mutations undergo apoptosis and are engulfed by macrophages, with resulting dark staining nuclear debris in their cytoplasm and are called “tingible body macrophages”. They are seen in many conditions like reactive lymphadenitis, follicular lymphoid hyperplasia and lymphomas.

Superantigens like Staphylococcal enterotoxins, TSST etc. activate a large number of T cells. TSST binds directly to Class II MHC without internal processing of toxin and the complex then interacts with the V beta chain on the TCR of multiple T cells. Activated T cells release IL 2 and macrophages release IL 1 and TNF causing shock.

Phytohemagglutinin or Concanavalin A are mitogens for T cells, and they stimulate T cells to divide while Endotoxin does not (only B cells divide with endotoxin).

Human T cells have a receptor for sheep RBCs and can form characteristic Rosettes with them.

ADCC or antibody dependent cell mediated cytotoxicity:* It is primarily mediated by NK cells. In the presence of a tumor or virus, the Fab domains of IgG antibodies bind specifically to antigens expressed on the surface of the tumor or virus-infected target cells, while the Fc domain of IgG antibodies bind to NK cell CD16 FcγR receptors, triggering the release of gamma interferon (IFN-γ), perforin, tumor necrosis factor alpha (TNF-α), granzyme B, interleukin-1 (IL-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to lysis of the cell.

Macrophages

• Origin from monocytes
• Types are alveolar macrophages, Kupffer cells (liver), microglia (brain), splenic macrophages, etc.
• Phagocytosis via Fc and C3b receptors
• Antigen presentation to Helper T cells with MHC II
• Produce IL 1, TNF, IL8
• Activated by interaction of microbes with TLRs and by Gamma Interferon produced by Helper T cells
• Attracted to sites of inflammation by C5a.

Natural Killer or NK cells

• CD 16+, 56+
• Produce gamma interferon
• Called large granular lymphocytes
• Activated by IL 12, alpha and beta interferons
• Role in ADCC
• MICA expressed on cancer cells is recognized by NK cells which then kills them
• Detect downregulation of MHC I in cancer cells and virus infected cells
• Secrete granzymes and perforins

Eosinophils

• Have receptors for IgE and IgG
• Granules have histaminase, leukotrienes, peroxidases and major basic protein (damaging to lung tissue in asthma)
• IL5 stimulates growth and differentiation
• Role in allergy and parasitic infestations

Fc receptors: They are receptors that bind to the Fc portion (in constant region), of the immunoglobulins and are present on immune cells like mast cells, macrophages, monocytes, neutrophils and NK cells. Pathogens coated with IgG and IgA are engulfed by immune cells by binding to the Fc portion of the antibody. Similarly, mast cells, basophils and activated eosinophils have receptors for Fc portion of IgE.

Types of immunoglobulins

IgM is the main Ig in primary response while IgG is predominant in the secondary response. IgG can opsonize bacteria. Only IgG types can be transferred across the placenta. Antigen specificity is determined by variable regions while function and isotype is determined by heavy chains. Secreted IgA can be monomer or dimer. J chain is a polypeptide chain that promotes polymerization of IgA and IgM.

Isotype: Differences in C regions of heavy chains Idiotype: Differences in variable or V regions Allotype: Different alleles of the same C gene

Other types of T cells

Suppressor or regulatory T cells: They can inhibit CD4 and CD8 T cells. They are CD25+. They produce FoxP3, a regulator of transcription and CTLA 4 which is an inhibitory surface protein. Mutations predispose to autoimmune diseases. Cytotoxic T cells: These are T cells, usually CD8 and sometimes CD4, that can kill other cells. They are important in the immune response to intracellular pathogens, viruses and tumor cells. They program their target cells to undergo apoptosis by preformed membrane pore forming perforins, and proteases called granzymes. Another mechanism of apoptosis is binding of Fas on the target cell membrane to Fas ligand expressed by activated cytotoxic T cells, which activates caspases. Cytotoxic T cells also release IFN alpha, gamma and TNF beta.

Tumor immunity: Tumor cells express novel antigens which are recognized by the immune system as foreign and attacked. NK cells, ADCC, cytotoxic T cells and macrophages are important in tumor immunity. Tumor antigens stimulate the production of antibodies, some are cytotoxic, but some are blocking antibodies which protect the tumor by blocking tumor antigens to prevent recognition by host immune cells.

Active Immunity: It is the immunity acquired after contact with foreign antigens like after clinical or subclinical infections, immunization with live or killed agents, exposure to microbial toxins or toxoids. It is long lasting but has a slow onset. Passive Immunity: Immunity from preformed antibodies like antitoxins/antisera to Diphtheria, tetanus, Rabies, Botulism, Hep A, B. Ig G passed from mother to child during childbirth. Ig A passed from mother to newborn in breast milk. Promptly available but short- lived. Risk of hypersensitivity Passive- Active Immunity: Administering both preformed antibodies and vaccine at the same time.

Complement deficiencies

Methods to assess function of immune cells

T cells form rosettes with sheep RBCs.

Complement is assessed by determining CH 50 which is the concentration of complement at which there is lysis of 50% antibody coated RBCs.

Types of grafts