1 / 48

Lecture 1 review

Lecture 1 review. Self vs. Non-Self. Recognize self Recognize the absence of self Recognize non-self Pattern recognition receptors Somatically generated receptors. The innate vs. adaptive immune systems (5). DIVERSITY OF RECEPTORS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS.

leo-larson
Download Presentation

Lecture 1 review

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lecture 1 review

  2. Self vs. Non-Self • Recognize self • Recognize the absence of self • Recognize non-self • Pattern recognition receptors • Somatically generated receptors

  3. The innate vs. adaptive immune systems (5)

  4. DIVERSITY OF RECEPTORS OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS

  5. Antigen – collection of ligands recognized by cells of both the innate and adaptive immune systems Epitope – smallest individually identifiable part of an antigen that is bound by a receptor

  6. Innate Pattern Recognition Receptors • How innate immune cells distinguish between microbes and self-cells? • How do they “know” if something is “dangerous” or not? (i.e. food, commensal organisms in the mouth and gut) • Use sets of highly conserved receptors that recognize patters of molecules shared by microbes – Pathogen-Associated Molecular Patterns (PAMPS)

  7. Hematopoietic Lineages

  8. Cytokines of Innate Immunity • Interleukins – produced and act on leukocytes • Chemokines– direct cell movement • TNF, IL-1- active vessels and recruit Neutrophils • IL-1 – Fever • IL-6 – Acute phase response

  9. Inflammation and local response • Activated innate cells trigger the process of inflammation: • Dolor (pain) • Calor (heat) • Rubor (redness) • Tumor (swelling) • Functio laesa (Loss of function; Immobility)

  10. Inflammation and local response • Release of vasodiolators = increased blood flow (rubor) and heat (calor) • Altered permeability (edema) = leakage of plasma proteins containing complement components, CRP, MLB, clotting factors • Leads to production of inflammatory cytokines (IL-1, TNF by macrophages) that trigger a whole range of effects designed to Recruit other cells to the site

  11. Local vs. systemic responses by innate immune system • Local inflammatory response can be mild, short-lived • May not even involve adaptive immune response • If infection is not contained, leads to systemic response, with more extensive consequences

  12. Natural Killer Cell Recognition

  13. Big picture: local innate immune responses

  14. Big picture: local innate immune responses

  15. Big picture: innate cell initiation of adaptive immune responses http://www.proteinlounge.com/Animation/Immune%20Response,%20Toll%20Like%20Receptors%20(TLR)%20Pathway

  16. Immunology - Lecture 2 Adaptive Immune System 1 Heth R. Turnquist, PhD E1542 Biomedical Science Tower 200 Lothrop Street turnquisthr@upmc.edu

  17. Molecules of the Adaptive Immunity - 6

  18. Adaptive Immune System • The adaptive immune system uses a broad range of molecules to function. • Some of the molecules used by the adaptive immune system are also used by the innate immune system. • Other molecules are specific to the adaptive immune system. • B cell receptor (antibodies) • T cell receptor • i.e. Ag – receptors • CD (Cluster of differentiation Molecules) – CD3, CD4, CD8, etc

  19. Immunoglobulins • Synthesized by B lymphocytes (B cells) • Synthesized and secreted by plasma cells – terminally differentiated B cells • Antibody is an immunoglobulin molecule with specificity for an epitope of an antigen. • Antibodies facilitate cells and molecules in the immune system to identify and interact with antigens. • Soluble antibodies are components of humoral (soluble) immune responses.

  20. Immunoglobulin (Ig) • Basic structure: • -4 polypeptide chains • 2 Heavy Chains • 2 Light Chains • -Called Ig Monomer • Variable domains on HC • And LC form epitope • Binding domain • Epitope = part of Ag • Fc - Region

  21. IgMonomers Contain 2 identical light chains and two identical heavy chains Binding site for each monomer is identical Diversity generated by different pairings of heavy and light chains

  22. Properties and Biological Activities of Immunoglobulin Isotypes IgM IgD IgG IgA IgE

  23. Ig and Complement Cascade (1) Interaction of antibody with antigen activates the classical complement pathway. Ag binding to epitope on Ag = change in Ab Fc region = C1q,r,s binding C1 components activate cascade culminating in MAC formation and cell lysis

  24. Ig and Complement Cascade (2) Interaction of antibody with antigen activates the classical complement pathway. Ag binding to epitope on Ag = change in Ab Fc region = C1q,r,s binding C1 components activate cascade culminating in MAC formation and cell lysis

  25. Major Histocompatibility Complex (MHC) • Tightly linked cluster of genes in all mammals • Called Human Leukocyte Antigen (HLA) complex • Gene products (3 classes) play a role in • Intercellular recognition • Discrimination between self and nonself • Important in cellular and humoral immunity • Acts as antigen presenting structures • The particular set of MHC molecules expressed by an individual influences the repertoire of Ag to which individual T cells can respond • May have a role in susceptibility to disease and in development of immunity

  26. MHC Class I, II, and III Located on Chrom 6; Human Leukocyte Antigen

  27. MHC Class I, II, and III Located on Chrom 6; Human Leukocyte Antigen

  28. 2 Types of MHC MHC class I – expressed on all nucleated cells MHC class II – expressed on APCs

  29. T Cell Receptor (TCR) T cells – each T cell expresses a unique, epitope specific cell surface receptor Heterodimers of two polypeptide chain Lack the capacity to initiate signaling to the nucleus capacity and rely on CD3 to transmit signals Unlike Ab – can not bind soluble Antigens. See peptides in context of MHC

  30. Two subsets of T cells interact differently with MHC: CD4+ T cells only interact with peptides bound to MHC class II CD8+ T cells only interact with peptides bound to MHC class I

  31. Cells and Organs - 7

  32. Lymphocytes • All originate from bone marrow • Named after place of “education” • Thymus-derived cells = T cells (CD3+ TCR+) • CD4+ T cells • CD8+ T cells • Bone-marrow-derived cells = B cells (BCR+ CD19+) • B cells – BCR+ cells • Plasma cells – terminally differentiated B cells producing Ig and no longer displaying it on surface • Natural Killer Cells (CD3- BCR- CD56+) • Granular appearance due to perforin and granzyme • Develop in BM – no education in Thymus

  33. CD4+ T cells • Comprise two thirds of all T cells • Recognize antigen in complex with Class II MHC molecules • Provide helper function

  34. CD8+ T cells • Comprise one third of all T cells • Recognize antigen in complex with Class I MHC molecules • Potent cytotoxic functions • “Cytotoxic T cells”

  35. B cells • Mature in the bone marrow • Express membrane bound antibody (Ig) on surface • Recognize soluble antigen

  36. When Ab on the surface of a B cells binds antigen for the first time, the B cell begins to divide rapidly to become a Plasma cell – secretes antibody; Small amount of membrane Ab; life span of a few days Or Memory cell – identical membrane antibody as on parent B cell, longer life span

  37. Natural Killer (NK) and • Natural killer T (NKT) cells • bridge the innate and adaptive • Immune systems. • NK Cells • Granular lymphocytes • No expression of TCRs • No expression of BCRs • Express receptors for: • 1. Stress molecules (KARs) • 2. MHC class I molecules (KIRS) • NK T cells • Express low levels of TCRs withlimited repertoires

  38. Lymphoid tissues and organs - Primary Lymphoid organs • Primary Lymphoid organs – Place where T and B cells learn to see self from non-self • Thymus: Bilobed organ where“prothymoctyes” from bone marrow turn into T cells • Where T cells aqcuire CD4, CD8, TCR • Self reactive cells removed

  39. Thymic Education of T cells

  40. Lymphoid tissues and organs - Primary Lymphoid organs • Bone Marrow: lymphocytic lineages that become B cells stay and undergo differentiation here • If early IgM on surface recognizes “self” they undergo apoptotic death

  41. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs • Lymphatic circulatory system • Cardiovascular system is responsible for circulating the soluble and cellular components of the immune system • Collection/filtration in the spleen

  42. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs • Lymphatics – Extensive capillary network that drains the tissues and collects lymph • Lymph = watery clear fluid that contains leukocytes and cells debris • Drainage system to remove cellular debris and microbes from the body’s tissues to the lymph nodes

  43. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs • Spleen – Largest lymphoid organ • Clears particulate from blood • Concentration of Ag and microbes • Lots of T cells and B cells (making antibody) Lots of Macrophages – dead cell removal

  44. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs • Lymph nodes – places of leukocyte accumulation and lymph filtration

  45. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs • Mucosa associated lymphoid tissues (MALT)

  46. Lymphoid Organs and Tissues

More Related