Immunogenetics. Immunodeficiency

Transcription

1 Immune response represents a system of recognition of foreign molecules. Immunogenetics Foreign molecules (proteins, glycoproteins, carbohydrates, ssdna, viruses) or parts of foreign molecules are called antigens. When foreign molecules enter in bloodstream immune system starts specific recognition of antigens and their destroying. omponents responsible for immune response: B (bone) T (thymus) macrophages Each type of ensures synthesis of different proteins responsible for immune response. 3 Type Deficiency of B- Deficiency of T- Deficiency of B- and T- Immunodeficiency Origin Genetic defects in maturing of B- Genetic defects in maturing of T- Mutations in genes for interleukins, deficiency of ADA (adenosindesaminase), absence of MH onsequence Viral infections Intracellular infections SID (Severe ombined Immune Deficiency) any pathogen 4 Macrophage deficiency Mutations in genes coding subunits of cytochrome B hronic granulomatosis (intracellular digestion absent) omplement deficiency Affected complement High susceptibility for infections 5

2 Humoral Determined by B- ; Mediated by antibodies. Immune response ellular Determined by T-; Mediated by TcR. Humoral response Production of Ab responsible for recognition of Ag. Ag interact in bloodstream with Ab and produce complexes Ab- Ag; omplexes Ab-Ag interact with other components of immune system: Ab-Ag is recognized by complement - 0 proteases, which destroy complexes, or Ab-Ag is recognized by macrophages, which destroy complexes. For secretion of Ab an interaction between B-cells with specific type of T-cells, called T-helper is required. 7 8 B-cell ellular response Antibody Secretion of antibodies, mediated by T-helpers Antigen Antibody-antigen complex Determined by T-, called cytotoxic T- cells (T-killer). Takes place in case of: Infections Reaction of tuberculine Rejection of tissues. Viral Ag are exposed on surface of the cell by, MH (major histocopatibilitycomplex). omplexes MH-Ag are recognized by T-cell receptors (TcR). Macrophage omplement 9 0 Infected cell Antigen + MH TcR!!! both Ig, and TcR never attack self protein tolerance. If organism loose tolerance autoimmune disease. T-killer cell

3 Main principles of immune response After contacting an Ag, organism become immune. It is resistant to repeated attack.. Antigen X Organism contains T and B immature. Each type of lymphocyte is able to produce a single type of antibody or TcR. Under antigenic attack Ab ortcr of some clones interacts with foreign molecules: These clones rapidly proliferate producing immune molecules (primary immune response); lone selection After antigen is destroyed, these cells are transformed in memory cells. Under repeated attack of the same antigen, memory cells are activated rapidly and produce secondary immune response. Antibodies anti-x 3 4 Ab ortcr interact with a fragment of antigen (5- amino acids). May be several types of against the same antigen; among them one is the most effective. Genes for immune system represent a superfamuly of immune genes: Genes for Ab Genes for TcR Genes for complement Genes for MH... These genes developed by repeated duplications of an ancestral gene. 5 Structure of antibody There are types of antibody in organism. Each antibody represents an immunoglobuline which consists of: identical L-chains (0%) λ (40%) identical H-chains. Each chain contains: N variable end (V) constant end ()

4 There are numerous gene segments (V and ) for each type of polypeptide dispersed in chromosomes, 4 and. Segments of immunoglobulin genes For synthesis of polypeptides junction of V and segments is required during somatic recombination between sister chromatids. Family κ(kappa) hrs. p % 0 V 300 J 5 D 0 Arrangement of different V and segments is different among different lymphocyte clones as well as STEM cells and somatic cells. λ(lambda) H (Heavy) q 4q Genes for immunoglobulin contain: Many segments for variable region (V), Junction segments (J), Diversity segments (D) Segments for constant region() J J J Recombination 5 J J Transcription 5 J 5 3 RNA processing AAAAAAA 5 Translation Polypeptide processing IgL Lambda J J J J J J D D D D J J J J J J Recombination st recombination J J J J J D D DJ J 5 99 J Transcription J J J J RNA processing J 5 AAAAAAA Translation 3 5 nd recombination Transcription RNA processing 3 5 AAAAAAA Polypeptide processing Translation IgL Kappa 3 Polypeptide processing IgH 4 4

5 Antibodies activate in different environment. Type of antibody is determined by variant of segment in H-chain. There are 5 types of H, so 5 classes of antibodies. Type H-chain % Function Main classes of antibodies IgM μ 5% Activates the complement IgD δ % IgG 80% Tolerance Activates the (in complement membrane) γ IgA α 4% In secrets IgE ε <% Allergic response 5 Mechanisms of antibody diversity Existence of many gene segments Somatic recombination Alternative splicing Polyallelism Allelic exclusion Erorrs of recombination Somatic mutations MH (Major Histocompatibility omplex) Multigenic, polymorphic system Located on p important in activation of cellular immune response Important for transplantation There are 3 types of genes 7 8 st lass HLA A, B, genes which encode Ag on surface of all cells nd class Surface Ag HLA D on macrophages, activated B, T- 3 rd class Seric proteins, membrane receptors involved immune reactions (Bf,, 4 factors) Heterogeneous proteins(hsp, TNF,β) Interferon Variable proteins, M=5-30 kda Synthesis induced by antigens Have nonspecific antiviral activity, inhibition of viral proteins, but not self Activate macrophages

6 Immune tolerance Immunodeficiency Inability to recognize as foreign antigens, which are not self Interaction with Ag during foetal development Absence or abnormal activity of components of immune system May be primary or secondary Primary may be hereditary or acquired 3 3 Immunodeficiency Increased susceptibility to some pathogens Severe infections Tumorogenesis Autoimmune diseases Autoimmune diseases Absence of tolerance to self antigens Production of self-antibody 33 34