Basic Immunology

1. Basic Immunology Dr Eman MS Muhammad

2. Immunity is defined as the resistance of the host to invasive pathogens & their toxic products. Immunology is the study of the components and function of the immune system. Definition of Immunity:

3. 1. Non specificorinnateimmunity: It includes the general common protective mechanisms against infection. It is the first line of defense & most pathogens are checked before giving rise to infection. It is always present; doesn’t change over time. If this line is breached adaptive immune system is called upon. Types of immunity:

4. Mechanisms: A. Mechanical: • Intact skin • Most mucosae using: • reflux mechanisms; eg coughing, sneezing & vomiting. • upward movements of respiratory tract cilia. • downward propulsion of intestinal contents. • constant flow of sterile urine. • tears.

5. Chemical: • Secreted fluids contain factors → killing & inhibiting of micro-organisms e.g: • sebum (secreted by sebaceous glands) is an antimicrobial. • blood, tears, saliva & intestinal fluids are rich in enzyme lysosome & other antibacterial. • protective proteins in blood & body fluids e.g: complement, c-reactive protein & interferon. • pH of gastric acid, bile & pancreatic secretions are hostile to micro-organisms.

6. Cellular: • Cells contributing to non specific immunity are: • Leucocytes: PML, macrophages, eosinophils → phagocytosis. • PML, macrophages, basophiles & mast cells→ secrete of soluble mediators of inflammation. • NK cells which are subpopulation of lymphocytes→ kill infected tissue cells

7. Features: • These mechanisms act rapidly during early stages of infections. • They can function in the absence of a specific immune response. • Many can be initiated or amplified by the specific immune system.

8. Specific (adaptive) immune system: • This system produces a specific reaction to each infectious agent & it normally eradicates that agent. • Furthermore, the adaptive immune system remembers that particular infectious agent & can prevent it causing disease later.

9. Features of the specific immune response: 1- Specificity: Infection with one organism → protection only against that organism or closely related organisms. 2- Memory: Once an immune response (Ir) against a particular microbe has occurred, protection against second infection with the same organism is usually a lifelong.

10. 3-Amplification: The ability to develop an enhanced response on repeated exposure to the same antigen. 4- Self & non-selfdiscrimination: It is the ability to discriminate between self & non-self components. Although the body occasionally recognizes self components as foreign → autoimmune diseases. Exposure to self components during fetal life → a state of a specific unresponsiveness, known as “immunological tolerance”.

11. Mechanisms of adaptive immunity: • Specific Ir is triggered by substances known as “antigens” & the resulting response is divided into: 1- Humoralimmuneresponse: • Result in the synthesis of antibody (Ab) molecules which react with the triggering antigens “active immunity”. • The protective effect of Ab can be transferred by injecting the serum of an immune individual to a non-immune individual “passive immunity”.

12. 2- Cellular immune response: It is independent on Ab protection. It is mediated by T lymphocytes. It includes active and passive types too. It can be transferred only by lymphocytes. NB:The normal Ir to infection involves both forms of immunity & is a complex process involving co-operation between lymphocytes, macrophages & other cells.

14. Adaptive Immunity: active and passive

15. Comparison of the main features of the innate & adaptive immune response:

16. Comparison of the main features of the innate & adaptive immune response:

19. Cells of the Immune System

21. Cells of the Immune System

22. Cellular basis of immune response • Allspecificimmuneresponsesare dependent on lymphocytes. • Antibodies are produced by “ B-lymphocytes”, while the cellular immune responses are initiated by “T-lymphocytes”. • All lymphocytes are derived from a common hematopoietic precursor cell in the yolk sac or liver during fetal life or bone marrow after birth.

23. The precursor cell differentiation & maturation occur either: in the bone marrow itself →B-lymphocytes. in the thymus →T lymphocytes. These tissues (B.M, yolk sac, fetal liver & thymus) are known as “Primary lymphoid organs (central)”, in which T and B lymphocytes mature and become competent to respond to antigens.

24. Both humoral & cellular immune response require a single resting or “virgin lymphocyte”to be linked to a unique antigenic determinant by a specific receptor & give rise to identical daughter cells which retain the antigenic specificity of the initial progenitor. These new cells comprise clone & this clonal proliferation ensures “amplified”& rapid Ir without loss of specificity.

25. Proliferation & differentiation of either B cell or T cell clones result in populations of an “effector cells”whose function is antigenic elimination. In the B-cell system, these effector cells are antibody producing cells “plasma cells”,while in the T cell system the effector cells are; cytotoxic T cells & T cells that produce delayed type of hypersensitivity reaction “T helper cells”. T cell differentiation also produces lymphocytes with regulating function e.g: “suppressor T cells”.

26. Clonal proliferation of both T & B cells results in populations of antigen specific memory cells whose function is to respond rapidly in “secondary immune response”. The cellular events which occur during & after recognition of antigen occur in the “secondary lymphoid organs (peripheral)”,in which adaptive immune responses to various antigens are initiated . They include lymph nodes, spleen, tonsils, Payer's patches & appendix.

27. Factors affecting the immune response: The form taken by the Ir depends upon: • The antigen: • its nature • route of entry • dose administered • Genetic constitution of the individual.

28. 1- Antigen (Ag) • Definition: • An antigen is a substance which is capable of interacting with products of the specific immune system such as Abs or the antigenic receptors on lymphocytes.

29. Properties: • large molecule • molecular weight more than 3 KDs • rigid in structure • protein or carbohydrate with or without other constituents e.g: lipid.

30. Antigen/antibody (Ag/Ab) reactions are the result of stereo-chemical interaction between molecules of complementary configurations & analogous to the interaction of a lock & key. Although all Ags are capable of forming such interactions, not every (Ag/Ab) can initiate an immune response after entry into the body. To do this an antigen must be immunogenic.

31. Immunogene: • It is an Ag that can trigger an Ir by cross linking Ag specific receptors on lymphocytes. • An Ag may fail to be immunogenic because it is not large enough to cross link receptors, or because the appropriate lymphocyte can not respond to the triggering signal. • Althoughsome small molecules, such as PABA, are not by themselves immunogenic, they may become so if they are attached to large molecules, such as serum albumin. • In these circumstances the small molecule is said to be a “hapten”.

32. Hapten: • It is a substance which can not induce an immune response by itself, but it becomes an antigenic when is attached to a protein. • Macro-molecular Ags have a complex surface to which each Abs of many different specialties can bind. • The site to which each Ab molecules binds an Ag is called “An Antigenic determinant or epitope”. However, the steric consideration limit the number of Ab molecules that can combine to an Ag at any time.

33. ValenceofanAg: • It is number of Abs that can bind to an Ag at saturation & it is usually less than the number of epitopes on an Ag. • Epitope: • Small part of an antigen that interacts with an antibody; 10-12 amino acids. • Any given antigen may have several epitopes. • Each epitope is recognized by a different antibody.

34. Epitopes: Antigen Regions that Interact with Antibodies

35. Route of Ag administration: • It affects the Ir both quantitatively & qualitatively. • This is probably due to Ag encountering different types of accessory cells involved in Ag presentation. • The subcutaneous, intramuscular & intradermal routes usually →strong Ir, while intravenous (IV) route →weak Ir & is also liable to induce specific immune tolerance. • Mucosal Ir is usually restricted to mucosal surface, while parentral route of Ag entry rarely stimulates mucosal immunity.

36. Dose of Ag administered: • The greater the dose of Ag administered, the greater the Ir. • However, extremely low or high doses of Ags may induce low dose tolerance & high dose tolerance respectively.

37. 2- Genetic constitution of the individual • Immune response depends on several genetically determined factors including: • various Ag binding sites found on both Abs & surface receptor of T cells. • immunity may also be determined by genes which control non-specific immune factors e.g: the phagocytic power of macrophages.

38. specific Ir genes are located within the major histo-compatibility complex (MHC) which is lies within a long stretch of DNA on the short arm of chromosome No. (6). • Ir genes do not encode the Ag binding sites of Abs or T cells, but influence the presentation of Ag to these cells.

39. Tissue Antigens • The major histo-compatibility complex (MHC): • It comprises a series of tightly linked cluster of genes encoding a group of highly polymorphic cell membrane glycoproteins. • In man, these MHC antigens are called human leucocyte associated antigens (HLA-Ags). • MH genes play roles in:

40. Central role in immune recognition. • Central role in development of humoral and cell-mediated immune response. • Critical role in antigen recognition by T cells. • MHC products are associated with intracellular recognition and self/non-self discrimination. • Major role in determining whether transplanted tissue will be histo-compatible or histo-incompatible.

41. MH gene complex comprises three groups of genes, designated MHC class I, MHC class II, and MHC class III.

42. Chromosome 6: HLA region

43. TheclassIAgs: • MHC Class 1 is found on all nucleated cells. • They mediates immune responses against endogenous antigens; antigens that are already found in the cell. • Usually, these cells that are expressing MHC class 1 are viral-infected or are tumor cells. • MHC Class 1 presents peptides that are 8 – 10 amino acids in size, which will then be recognized by the cytotoxic T cells.

44. MHC Class 1 are encoded by genes in the A, B, C regions of the HLA locus. • As class I alleles are expressed co-dominantly, tissue bears the Ags of both parents.

45. TheclassIIAgs: • MHC class 2 mediates immune responses against exogenous antigens; antigens that are found outside the cell. • MHC class 2 will bind with amino acid residues that are 13 – 18 in size and will be recognized by T helper cells. • The MHC class 2 protein is found on cells like the B lymphocytes, macrophages, monocytes, dendritic cells, and endothelial cells. • These cells are phagocytic and can engulf an extracellular antigen. • MHC class 2 Ags are involved in the presentation of Ag to T-cells.

46. Sometimes they are referred to as “immune associated antigens”, or (Ia-Ag). • They are encoded by genes in the HLA D region which consists of at least 3 major loci; DP, DQ & DR. • Some other cells can express class II Ags facultative particularly when stimulated by interferon y. • Like class I Ags; class II alleles are expressed co-dominantly.

47. The class III complex: • Class III complex generally encode secreted proteins associated with the immune process. • These are secreted protein molecules which include several complement components (C2, C4), certain cytokines (TNF-α, TNF-ß) & certain enzymes (steroid 21-hyderoxylase). • Reason for location within the MHC region is uncertain

48. HLA antigens & diseases: • A variety of diseases are associated with certain HLA types. • The best known is the association between ankylosing spondylitis & HLA-27. • The diseases that have association with HLA can be grouped into: • Inflammatory diseases:including ankylosing spondylitis & post-infectious arthropathies. All associated with HLA B27.

49. Inherited errors of metabolism:e.g: 21-hydroxylase deficiency (HLA BW27). • Autoimmune diseases: including autoimmune endocrinopathies- associated with alleles at the DR locus e.g: Type I diabetes (DR3, DR4). • The mechanisms underlying these associations are not fully understood.

50. Complement system • It is a group of proteins in the blood which interact with each other & with other components in the innate & adaptive immune system. • It is the major effector of humoral branch of the immune system. • They are synthesized by hepatocytes, blood monocytes, macrophages & some epithelial cells.