Immunity

1. Immunity Lange chapter 57 Samuel Aguazim(MD)

3. Definition and general description of the immune system • Immunology: Study of the body’s defense system against illness and invasion by things foreign to it. • Protection from diseases especially infectious diseases • For survival and reproduction organism must: • Interact with environment • Recognize and respond to external and internal threats

4. The charge of the immune system • To defend the body against the internal and external threats • Performance depends on: • Ability to distinguish between self (or that which is identical to self) and non self • Ability to identify threatening and non threatening situations • Ability to respond appropriately

5. The charge of the immune system • Immune system constantly guards against: Infectious organisms • Parasites • Toxins (toxic substances) from other organisms or environment • Cancer • Non compatible tissue grafts • Different mechanisms are required against different types of pathogens

6. The charge of the immune system • Serves like an armory for tools and weapons of defense • As army able to use both the tools and weapons against pathogenic attacks

7. The weapons and tools for use to defend the host • They are cellular, molecular and tissue components • Each has at least a deadly effect, many have multiple • They are wielded ferociously • In the constant state of war between would-be pathogens and the human host. • Leading to destruction and degradation often of the invading organism

8. The weapons and tools for use to defend the host • They are cellular, molecular and tissue components • Each has at least a deadly effect, many have multiple • They are wielded ferociously • In the constant state of war between would-be pathogens and the human host. • Leading to destruction and degradation often of the invading organism

9. Overview of the Immune System Interactions between the two systems

10. Anatomical barriers- mechanical

11. Anatomical barriers- mechanical

12. Immune system Cells of the immune system • Myeloid cells • Lymphoid cells • Granulocytic • Monocytic • T cells • B cells • NK cells • Neutrophils • Basophils • Eosinophils • Macrophages • Kupffer cells • Dendritic cells • Helper cells • Suppressor cells • Cytotoxic cells • Plasma cells

13. Organs of the Immune System… • APCs, T-cells and B-cells populate Lymphoid Tissues… • Lymph nodes • Spleen • Peyers Patches et al… • (+Thymus and Bone Marrow) • …& travel via the Blood and Lymph…

14. The Big Picture of the immune System • The system is highly regulated to ensure proper functioning • There is a wide range of pathogens threatening the human body • Different immune mechanisms are required to fend off different types of pathogens • Normally discriminates against non-self and recognizes self and does not act against self • The human immune system is made up of two major branches

15. The Innate and Adaptive immune systems • Human body uses two immune systems against infectious agents • A) The innate (also called “nonspecific”, “natural" or “native”) immunity • An ancient system of self defense • Always present in healthy individuals • Ready to block entry of microbes to the body • Promptly eliminates microbes that succeed in entry

16. Innate immune system • Innate (or natural) immunity • This is made up of several components. They recognize and respond to microbes, damaged host cells by microbes but do not react against nonmicrobial agents. They encode and synthesize pattern –recognition receptors (PRRS)by a variety of white blood cells, able to recognize and bind molecules of other groups like bacteria etc.

17. Innate immune system • Physical barriers are the first line of defense against infection. The skin and mucous membranes provide a continuous epithelia for our body surface, gastrointestinal tract and the respiratory tract which are the common portals of microbial entry. They are backed up with mechanical protection through cilia and mucous. They must be breached for infection to take place.

18. Physiological factors such as pH, temperature and oxygen tension limit microbial growth. The acid environment of the stomach and vagina, the free fatty acids of the skin, peptide antibiotics of the epithelial cells combined with microbial competition from the normal micro biota (microbial antagonism) inhibit infections in the respective anatomical sites

19. Innate immune system • Protein such as Lysozomes secreted into external body fluids also help resist invasion. Soluble factors within the body such as Complement, Interferons and collectinsand other "broadly specific" molecules such as C-reactive protein are of considerable importance in protection against infection.

20. Innate immune system • Phagocytic cells are critical in the defense against bacterial and simple eukaryotic pathogens. Macrophages, dendritic cells,polymorphonuclear leucocytes (PMN), intra epithelial lymphocytes and the natural killer cells(NK) can recognize bacterial and yeast cell walls and infected or stressed host cells through broadly specific receptors (usually for carbohydrate structures) and this recognition is greatly enhanced by activated complement (opsonin).The receptors recognize in a broad and general the presence of infectious agents

21. Innate immune system • Acute Inflammation: The acute inflammatory response phase (the initial response of the body to harmful stimuli achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues is a major part of the innate immune system. Many infections, especially where small wounds are the route of entry, are eliminated by the combination of complement and recruitment of phagocytes, which flow from the acute inflammatory response. • A hallmark of the innate immune system is that it has no memory of a previous encounter with a foreign organism. The system is good at dealing with extracellular bacteria, fungi and intracellular viruses.

22. The Innate and Adaptive immune systems B) Adaptive (or specific or acquired) immunity Stimulated by the microbes that invade the body Consists of lymphocytes with receptors that recognize different substances produced by microbes and noninfectious molecules Triggered only if microbes or their antigens pass the innate system to get to the lymphoid organs to be recognized by lymphocytes The innate and adaptive systems work together to develop protective immunity

23. Adaptive immunity • The first encounter with an antigen is known as the primary response. Re-encounter with the same antigen causes a secondary response that is more rapid and powerful.

24. Adaptive immunity • Types of adaptive immunity: • There are two types, humoral and cell-mediated. Both of them work together but the effector mechanism depends on the characteristic nature of the antigen

26. Humoral immunity • ● Humoral immunity is mediated by proteins called anti bodies secreted by B lymphocytes into the circulation and mucosal fluids to neutralize and eliminate bacteria and their toxins in the lumens of organs like the GIT and also to prevent mucosal attachment by microbes. In this way, antibodies stop the establishment of infections in such organs. Antibodies work in three ways.

27. Humoral immunity • Neutralisation. blocking the biological activity of their target molecule e.g a toxin binding to it's receptor • Opsonisation. interact with special receptors on various cells, including macrophages, neutrophils, basophils and mast cells allowing them to "recognize" and respond to the antigen • Complement Activation. cause direct lysis by complement which also recruits and enhances phagocytosis

29. Cell Mediated Immunity • is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells, the production of antigen-specific cytotoxic T-lymphocytes, and the release of various cytokinesin response to an antigen. Cellular immunity protects the body by :

30. Cell Mediated Immunity • 1. activatingantigen-specific cytotoxic T-lymphocytes (CTLs) that are able to destroy body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens; • 2. activating macrophages and NK cells, enabling them to destroy intracellular pathogens; and

31. Cell Mediated Immunity • 3. stimulating cells tosecrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.

32. Cell Mediated Immunity • Cell-mediated immunity is directed primarily microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoan, cancers, and intracellular bacteria. It also plays a major role in transplant rejection.

33. Recognition by the innate immune system is required to trigger adaptive immune responses. Innate Immunity No adaptive specificity, no memory Mucous membranes, phagocytes (RES), complement, anti-bacterial peptides… Adaptive Immunity Specificity, memory B-Cells, T-Cells

34. Ag uptake by APC Afferent Ag Processing & Display Ag Presentation, … APC/T-Cell interaction Ag-specific triggering of B- and T-Cells; Proliferation & differentiation Central Effector functions: TC –target cell killing TS/R – Suppression/regulation; Tolerance Efferent TH1/DTH – Delayed Type Hypersensitivity TH2/B-cells, Ab killing/inactivation of targets Complement, killing & immune complexes Three Limbs of the Immune Response

36. Blood monocyte (Phagocytic, APC)

37. (T-cell, B-cell, or…) Blood lymphocyte

38. Primary and secondary antibody response IM-07 Positive and negative T cell selection in

39. Humoral Immunity (HI) Transferred by serum – mediated by antibodies Cell-Mediated Immunity (CMI) Not transferred by serum – mediated by T-cells (& other inflammatory cells)

40. When the Immune System Goes Wrong… • Infection (bacteria, viruses, other parasites) • Immunodeficiency (congenital, acquired, iatrogenic) • Allergy (food/animals/drugs, hay fever & asthma…) • Autoimmune disease (rheumatoid arthritis, lupus etc.) • Contact dermatitis (poison oak, affordable jewelry) • Transplant rejection (kidney, heart, lung, liver etc.) • Transfusion reactions (blood typing)

41. effector functions