Immunity

Immunity: host or bodys response to antigen Defense against invading pathogens Removal of 'worn-out' cells & tissue debris Identification & destruction of abnormal or mutant cells Rejection of 'foreign' cells Cells of immunity Leukocytes: leuko (white) cyte (cell); white blood cells (WBC) 4,500-10,000 cells /mm3 Primary cels involve in immune resonse Mobile, able to detect, attack and destroy anything foreign Leukocytosis: elevated WBC count Leukopenia: decreased WBC count

Types of Immunity INNATE/ NATURAL/ NON SPECIFIC Innate/ native/ inborn/ nonspecific Present at birth Responds rapidly Gives the same response to all antigens No immunologic memory 1st line Defeses: practically epithelial barriers to keep pathogens out Skin Respiratory tract Gastrointestinal tract Tears, nasal secretions and saliva Sperm

2nd Line of Defenses Phagocytic Cells: Cells that eats up foreign substances Monocytes/ macrophages Largest and most efficient phagocytic cell : makros:large and phagein:eat Leaves the bone marrow as a monocyte and transforms(differentiate) into macrophages when it reaches the tissues Resident macrophages: Dust/ alveolar macrophages Alveoli/lungs Kupffer cells liver microglia brain histiocytes Connective tissues Osteoclasts Bone marrow Epitheloid granuloma Sinusoidal lining cells spleen Chronic infection, viral and intracellular parasitic infection

Granulocytes: contain granules seen under a microscope Neutrophils Polymorphonuclear leukocytes (PMNs) 55-70% of leukocytes: most abundant Bands: immature neutrophils o Round/ kidney shaped nucleus o 5% Segmented: mature neutophils o Segmented nucleus o 55% Quickest response Effective against bacteria and fungi Eosinophils Name attributed to its affinity towards a red dye called eosin 1-4% Respiratory and GI Effective against parasite and hypersensitivity/allergic response Basophils Named attributed to its affinity to basic dye which is bluish in color 0.5-1%:Least common granulocytes Similar to mast cells: contains histamine and heparin Plays a role in parasitic (ectoparasites) and allergic reactions Dendritic cells Star-shaped or dendrite appearance Probably arised from monocytes Langerhans cell dendritic cells on the skin Immature dendritic cells phagocytises antigens, Capture antigen and transport it to the lymph nodes Mast cells: (non-phagocytic) Paul Ehrlich in 1878 called it Mastzellen (German: mast = food) Found in the skin and mucosa of both respi and GI tract Mast cell degranulation refers to the release of chemical mediators (histamine, serotonin, tryptase, heparin, prostaglandin, leukotrienes, platelet activating factor, cytokines, eosinophil chemotactic factor) from its granules. Mast cell degranulation may be triggered by: o Direct injury to the mast cells o Activation by IgE o Activation by the complements Phagocytosis: Process of engulfing or eating up a microbe Phagocyte: white blood cells that ingest harmful bacteria, foreign cells, and dead or dying cells Phagosome: a cellular compartment containing an engulfed pathogenic microorganism which provides a place where it can be killed and digested Lysosome: part of a cell which contains acid enzymes that breaks up waste and debris Opsonins: any molecule that binds to the antigen that enhances binding of phagocytes to the pathogen Latin opsonare to buy provisions; to prepare a feast Opsonization: process of marking a pathogen for ingestion by a phagocyte Inflammation Causes:

Biologic response of a vascular tissue to injury Infection Physical trauma Chemical, irradiation, mechanical and thermal injury Immune reactions

Phases of Acute Inflammation

Chemical Mediators of Inflammation Mast Cells and basophils degranulate/ release chemical mediators or substances from its granules o HISTAMINE - vasodilation and increase permeability o SEROTONIN vasodilation and increase permeability o BRADYKININ vasodilation and increase permeability, pain o PROSTAGLANDINS- vasodilation and increase permeability, fever, pain o LEUKOTRIENES vasodilation and increase permeability, enhance endothelial stickiness, fever Macrophages release of cytokines
Cytokines: Group of protein molecules produced by cells of the immune system, acting as messenger or signalling cells to regulate the function of its target cells. Common Cytokines

Tumor necrosis factor (TNF)enhance endothelial stickiness, fever Interleukin-1 (IL-1) enhance endothelial stickiness, recruitment of macrophage from bone marrow, fever o Interleukin-6 (IL-6) , fever o Chemokines enhance endothelial stickiness Activation of complement system
Complement System Composed of about 20 proteins found in the serum The term complement refers to the ability of this protein to complement or enhance the effectivity of the antibodies. When activated each component activates the next in the series The series ultimately leads to activation of a protein that causes cell lysis Forms cleavage products that mediates immune responses Important Complements

o o

C3a-vasodilation and increase permeability, mast cell degranulation C5a vasodilation and increase permeability, mast cell degranulation
C3b C4 C56789

Functions of the Complements System Opsonization - enhancing phagocytosis of antigens Chemotaxis - attracting macrophages and neutrophils Lysis - rupturing membranes of foreign cells Altering the molecular structure of viruses Vascular Vasodilation and increase blood flow (hyperemia) Increase permeability Exudate formation: Fluid shifts out of the blood vessels into the interstitial space Formation of adhesion molecules where cells can hold on to

Cellular Margination: Movement of immune cells along the walls or endothelium of the blood vessels Adhesion: Leukocytes are able to attach or hold on to the endothelium of the blood vessels Pavementing: Once immune cells are able to establish a firm hold on the endothelium, more and more leukocytes migrate and adhere to the wall of the endothelium Diapedesis: Greek: leap or ooze through. Emigration of the leukocytes from the blood vessel into the interstitium Chemotaxis: cytokines attract the leukocytes to move towards inflamed area

Movement of proteins (leukocytes) and nutrients to the inflamed area increase the oncotic pressure in the interstitium which contributes to more edema Phagocytosis

Symptoms: Latin inflammare: to set on fire Cardinal Signs of Inflammation Rubor redness Calor- localized heat Tumor swelling Dolor pain Functio laesa loss of function due to pain and swelling Systemic Symptoms Fever and chills Body malaise Anorexia and weight loss Muscle and joint aches Lymphadenopathy Functions of Inflammation Perform temporary repair and prevent additional pathogen entry. Slow the spread of pathogens away from the area. Mobilize local, regional, and systemic defenses that can overcome the pathogens and facilitate permanent repair. To repair/replace tissue damaged by the injurious agent or its byproducts. Adverse Effects of Inflammation Tissue damage: prolonged inflammation causes increase number of dead pahagocytes which realeases their lysosomes on surrounding tissue Cy tokines release causes systemic manifestations: fever, anorexia, malaise, weight loss Pharmacology NSAIDS: prevents prostaglandin synthesis Salicylates: Aspirin Mefenamic Acids (Ponstan, Dolfenal, Gardan) Acetic Acid derivatives: Ketorolac, diclofenac Propionic acids: Ibuprofen (Advil, Dolan, Midol ), Naproxen (Flanax, Skelan) Oxicams: Meloxicam (Mobic), Peroxicam (Feldene) Selective COX Inhibitors: Celecoxib (Celebrex) Acetaminophen/ Paracetamol: prevents prostaglandin synthesis Corticosteroids: antiInflammatory Natural Killer Cells (NK cells) Mediators of innate/ natural immunity Able to determine whether a cell is infected or not Cannot form memory of antigen Perforins bores holes, granzymes are dump into the cell->cysteine proteases -> apoptosis Effective against viruses and tumors

Adaptive Immunity Adaptive/ specific Stimulated by antigens Slow to start Highly specific Has immunologic memory

Properties

of Adaptive Immunity Specificity Clonal expansion Specialization Memory Nonreactivity to self-antigens

Lymphocytes Key mediator of ADAPTIVE immunity (except NK cells) 20-40% T lymphocytes Mature in the T=thymus Mediates or causes cell mediated immunity T lymphocytes are comprised of: o Helper T-cells Also called CD4 T-cells Regulates other immune cells B-lymphocytes-> produce immunoglobulins Phagocyte/ Macrophages -> enhanced ability to destroy/ingest microbes Able to remember previously encountered antigen (Memory) o Cytotoxic T-cells Also called Cytolytic T-cells (CTL); Killer T-cells Also called CD8 T-cells Contains perforins, granzymes and granulysin Perforins bores holes, granzymes are dump into the cell->cysteine proteases -> apoptosis (programmed cell death) o Memory T-cells Reserved clones of T cells with previous encounter with an antigen Cell mediated Immunity Helper T-cells (CD4 Tcells) After recognition of antigen from MHC II on APC, it will make clones of itself. Some clones would remain inactive until activated by future exposure to same antigen Some clones will activate and stimulate: o B cells to produce to differentiate into plasma cells and produce antibodies o Enhanced phagocytosis by macrophages Cytotoxic T cells/ Killer T cells (CD8) Infected cells will get sample of antigen from microorganism in its cytoplasm Antigen will bind with MHC I molecule and present it on its cell membrane or surface Cytotoxic T cells will undergo clonal expansion Some clones would remain inactive until activated by future exposure to same antigen Cytotoxic cells bind with infected cells and release perforins and granzymes Humoral Immunity B lymphocytes Mediates humoral immunity Matures in the B-Bone marrow Differentiates to: o Plasma cells Produces immunoglobulins=antibodies (IgG, IgA, IgM, IgE, IgD) o Memory B cells Clones of activated B cells with same memory of parent cell that encountered the antigen Antigen is presented on an MHC II complex on an antigen presenting cell such as a macrophage Helper T-cells (CD4 T cells) binds with the MHC and releases cytokines

Cytokines released by the Helper T cell will activate B-cells to multiply (clonal expansion) A few clones will remain inactive until stimulated by exposure to the same antigen (Memory B cells) Most clones will differentiate to plasma cells Plasma cells produce antibodies or immunoglobulins Effects of Antibodies Agglutination Neutralization Precipitation Opsonization Lysis by complement activation

Type of Immunoglobulins Location IgG

Functions

Ig A IgM

IgE

IgD

Types of Immunity Natural: Formed naturally by the body/ born with it Acquired: obtained from an external source Passive: immune cells are transferred to a body and there is no need for it to form antibodies on their own/ the immunity is temporary based on the lifetime of the immune cells Active: formation of antibodies against the antigen Immunization Immunization: a process in which the human immune system is prepared against attack by infectious microorganisms Vaccination: administration of antigenic material (a vaccine) to produce immunity to a disease. Types of Vaccination: 1. By injecting dead organisms: no longer capable of causing disease but still have their chemical antigens (typhoid fever, whooping cough, diphtheria, and other bacterial diseases) 2. By injecting toxins: chemically treated so that their toxic nature has been destroyed even though their antigens for causing immunity are still intact. (tetanus, botulism, etc) 3. By injecting live, attenuated organisms: organisms have been grown in a special media or have been passed through a series of animals until they have mutated enough that they will not cause disease but still do carry the specific antigens. (poliomyelitis, yellow fever, measles, and other viral diseases).