Characteristics of B cell lineages
| B cell lineage | Characters |
| pro-B cell | Surface IgG absent, c-Kit and IL 7 receptor+ |
| pre-B cell | Intracellular and +/- surface mu chains |
| Immature B cell | IgM present as cell surface receptor |
| Mature B cell | IgM and IgD present as cell surface receptors |
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
| MHC Class I | MHC Class II |
| Expressed by all nucleated cells | Expressed by T cells, B cells, macrophages, Langerhans cells, dendritic cells, microglia, thymic epithelial and stromal cells |
| Present antigens to CD8+ T cells | Present antigens to CD4+ T cells |
| Consists of 4 domains - alpha 1,2, 3 domains of the alpha chain, and a beta 2 microglobulin; cleft between alpha 1 and 2 binds peptide antigen | Consists of 4 domains - alpha 1 and 2 of alpha chain, and beta 1 and 2 of beta chain; peptide antigen binds in the groove between alpha 1 and beta 1 domains |
| Binds peptide antigens that are 8-10 amino acids in length | Binds peptide antigens that are >13 amino acids in length |
| Coded by Class I loci A,B and C | Coded by Class II loci DP, DQ and DR |
| Presents intracellular antigens | Presents extracellular antigens |
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
| Properties | Dendritic cells | Macrophages | B cells |
| Antigens presented | Peptides, viral antigens, allergens | Intracellular and extracellular pathogens, particulate antigens | Toxins, viruses, soluble antigens |
| Mechanism of antigen uptake | Macropinocytosis, phagocytosis | Macropinocytosis, phagocytosis | Antigen specific immunoglobulin receptor |
Adhesion molecules involved in T cell function
| Adhesion molecule | Ligand |
| LFA 2 or CD2 | LFA 3 or CD58 |
| ICAM 1 and ICAM 2 | LFA 1 |
| ICAM 3 | DC SIGN (dendritic cells and macrophages) |
| VCAM 1 | VLA 4 |
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.
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
| Characters | Heavy chain | Activation of classical complement pathway | Activation of alternate complement pathway | Others |
| IgG1 | Gamma 1 | ++ | _ | Most abundant Ig in the serum |
| IgG2 | Gamma 2 | + | _ | |
| IgG3 | Gamma 3 | +++ | _ | |
| IgG4 | Gamma 4 | _ | _ | |
| IgM | Mu | +++ | _ | Heaviest, monomer on B cell surface, pentamer in serum; hinge region absent; highest avidity |
| IgA1 | Alpha 1 | _ | + | Secretory component protects IgA from degradation, involved in mucosal immunity, present in saliva, tears, breast milk, secretions, prevents microbes from attaching to mucosa |
| IgA2 | Alpha 2 | _ | _ | |
| IgD | Delta | _ | _ | B cell surface receptor |
| IgE | Epsilon | _ | _ | Hinge region absent, mediates immediate hypersensitivity, allergic and anti-helminthic responses |
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
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
| Complement deficiency | Clinical manifestations |
| C1q | Nephritis, photosensitivity, CNS involvement, increased susceptibility to encapsulated bacteria |
| C4 | Glomerulonephritis, increased susceptibility to encapsulated bacteria, autoimmune diseases like SLE |
| C2 | Photosensitivity, arthritis, pleural and pericardial involvement, increased pyogenic infections with encapsulated bacteria like Pneumococcal pneumonia, sepsis and meningitis, autoimmune diseases like SLE |
| C3 | Recurrent pyogenic infections |
| C5-9, membrane attack complex (MAC) | Neisserial infections |
| Mannose binding lectin or MBL | Pneumonia, meningitis and respiratory infections |
Methods to assess function of immune cells
| Cells | T cell | B cell | Phagocytes |
| Functional assessment | T cell proliferation in response to phytohaemagglutinin, tetanus toxoid, concanavalin A, pokeweed mitogen, lipopolysaccharide, skin test | Induced antibody production in response to mitogens like pokeweed, serum immunoglobulin levels | NBT test (nitroblue tetrazolium ) |
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
| Graft | Description |
| Autograft or autologous graft | From self e.g. transplanting patient’s own skin from one area of the body to another |
| Allograft or heterologous graft | From another individual (within the same species) |
| Xenograft or heterograft | From other species e.g. pig to human |
| Isograft | Between identical twins |