Objectives Immunology 1

complement system - group of 20 proteins synthesized in the liver that complement the effect of innate immune system. Three pathways for activation--Classic, Lectin, and Alternative. All pathways end with C3b production, the central molecule of complement cascade which marks pathogens as foreign and targets it for destruction (opsonization).

Classic - requires antibody for activation. the complement binds to antigen-antibody complex (IgM or IgG). A cascade of enzyme cleavage and binding produces membrane attack complexes (MAC) which pokes holes in cells allowing cell contents to leak out. Lectin and alternative pathways are antibody independent

Pattern Recognition Receptors (PRRs)

Found on phagocytes, dendritic cells, endothelial cells, and lymphocytes Recognize and bind PAMPs Cells possess PRRs whether they have encountered PAMPs before or not

What is the role of antigen presenting cells in linking innate and adaptive immune systems through cytokine production? An APC, such as a macrophage, engulfs and digests a foreign bacterium. An antigen from the bacterium is presented on the cell surface in conjunction with an MHC II molecule Lymphocytes of the adaptive immune response interact with antigen-embedded MHC II molecules to mature into functional immune cells.

MHC I are found on all nucleated body cells, and MHC II are found on macrophages, dendritic cells, and B cells (along with MHC I) MHC class I presents to cytotoxic T cells; MHC class II presents to helper T cells / Cytotoxic T cells binds to MHC1 and helper T cells bind to MHC2

Functions of the complement system Destruction of pathogens Opsonization of pathogens Recruitment of phagocytes Immune clearance

Membrane attack - by rupturing cell wall of bacteria. Phagocytosis - by opsonizing antigens. C3b has most important opsonizing activity. Inflammation - by attracting macrophages and neutrophils.

Innate immune system: Monocytes Monocytes are short-lived myeloid cells that patrol the body throughout life, reacting to inflammation by rapidly entering inflamed tissue and differentiating into macrophages or dendritic cells on demand.

Monocytes and macrophages are professional antigen presenting cells (immune cells that specialize in presenting an antigen to a T-cell). They express class II major histocompatibility complexes (MHC), which can be recognized by helper-T cells. The main types of professional APCs are dendritic cells (DC), monocytes/macrophages, and B cells.

Innate immune system: NK Cells Act as an immediate nonspecific response to virally infected and malignant cells Kill virus-infected cells and tumor cells through the secretion of cytotoxins (Ex. perforins and granzymes, which work to induce apoptosis) Produce gamma interferon (INF-𝛄) to activate macrophages to kill bacteria

Recognize abnormal cells without antigen presentation Induce cell apoptosis with or without antibody Activate macrophages via gamma interferon

Innate immune system: Eosinophils

Release chemokines, cytokines, and lipid mediators Important role in inflammatory response triggered by allergies, asthma, parasites and helminthic infections

Innate immune system: Macrophages Differentiated from monocytes. Three main functions include phagocytosis, antigen presentation, and cytokine production. Cytokine production: (tumor necrosis factor - TNF, Interleukin-1 - IL-1, Interleukin-12 - IL-12)

Resident macrophages arrive before birth, are fixed, and are the first cells to respond to foreign invaders or injured tissues. Ex. lungs → alveolar macrophages; bone → osteoclasts; liver → kupffer cells; CNS → microglia cells. When a macrophage encounters an outsider, it extends its cell membrane around the particle, drawing the particle into itself. It then forms a vesicle called a phagosome. Lysosomes inside of the macrophage release enzymes that break apart the captured particle inside of the phagosome.

Innate immune system: Platelets Platelets contain a number of integrins and cell adhesion molecules on their surface which bind to both leukocytes and endothelial cells and help capture flowing leukocytes from the circulation. Inflammation: secretes cytokines (IL-6, IL-8), chemokines, and platelet derived growth factor (PDGF). Immunothrombosis: Platelets contain infection in clot Dendritic cells are found in tissue that has contact with the outside environment such as the over the skin (present as Langerhans cells) and in the linings of the nose, lungs, stomach and intestines. Immature forms are also found in the blood.

The first line of defense is initiated when cellular pattern recognition receptors (PRRs) located on antigen-presenting cells (APCs) recognize pathogen-associated molecular patterns (PAMPs). Recognition of PAMPs by PRRs rapidly triggers the innate immune response characterized by an induction of various inflammatory cytokines and chemokines. Several families of PRRs, including Toll-like receptors (TLRs), NLRs, and RLRs, are known to play a crucial role in host defense. Over time APCs can activate the adaptive immune response to the invading pathogens by triggering T cells.

Innate immune system: Neutrophils First leukocyte to arrive at site of infection. It removes the foreign invader by phagocytosis and signaling the inflammatory response.

50-70% of circulating leukocytes. Chemokines: attract other leukocytes to site of infection

Innate Immunity: Inherited from the parents, i.e. pass from one generation to other. It is a non-specific and rapid response, no specific memory associated. Antibodies are not produced. Acts by providing barriers that prevents the entry of pathogens in body. Antigen presenting cells have pattern recognition receptors (PRRs) that recognize PAMP on pathogens

Adaptive Immunity: Acquired during the exposure to different pathogens and through vaccinations after birth. It is specific, memory is associated. It acts by production of specific antibodies against the pathogens. Primary and secondary immune responses are produced via T-lymphocytes and B-lymphocytes.

Innate immune system: Basophils and mast cells Contain surface receptors for immunoglobulin E (IgE) Secrete histamine (vasodilation), Interleukin IL-4, and heparin (anticoagulant) in response to various allergic reactions and parasites Release newly generated eicosanoids (lipid mediators!) - prostaglandins and leukotrienes

Basophils supplement the function of mast cells; basophils circulate in bloodstream whereas mast cell are fixed in tissue under skin and in mucosa of GI and respiratory tract Make up less than 1% of circulating leukocytes Play a role in anaphylaxis and anaphylactic shock - rapid degranulation may result in vasodilation and a sudden drop in BP