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The Immune System The body’s defense 1. Nonspecific 2. Specific

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Presentation on theme: "The Immune System The body’s defense 1. Nonspecific 2. Specific"— Presentation transcript:

1 The Immune System The body’s defense 1. Nonspecific 2. Specific
Cell mediated Antibody mediated

2 Three cooperative lines of defense have evolved to counter these threats.
Two of these are nonspecific - that is, they do not distinguish one infectious agent from another.

3 Nonspecific defenses “Nonspecific” = don’t have to recognize an invader to fight it Skin: physical barrier Sweat glands: chemical defense Mucous membranes: Line body openings- physical barrier Secretions: Antimicrobial proteins present in secretions Mucous traps particles Acid in stomach-destroy most except hept.A Chemical defense = ph is 3-5, dry acidic environment is intolerable to bacteria

4 Besides being a physical barrier, the skin and mucous membranes chemically destroy pathogens.
Secretions from oil and sweat glands give the skin a pH ranging from 3 to 5, acidic enough to kill most microbes. Growth is also inhibited by saliva, tears, and mucous secretions that continually bathe the exposed epithelium. All these secretions contain antimicrobial proteins. One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them.

5 2ND LINE-Internal Microbes that penetrate the first line of defense face the second line of defense, which depends mainly on phagocytosis, the ingestion of invading organisms by certain types of white cells. Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins.

6 Second line of defense cells function like roaming patrols
1. Nonspecific defenses of chemicals and cells-Stimulated by cytokinnins 2. Act rapidly with infection 3. Employ negative test that cannot be foiled by copycat foreign cells

7 4. All cells possess major histocompatibility complex (MHC) proteins
5. Different in each individual. Distinguish self from non self. Due to MHC proteins-before birth 1. MHC 1-nucleated cells-body cells 2. MHC II- Nucleated cells-macrophages-B cells-some t cells a. 50 alleles-20 genes b. In autoimmune diseases defensive cells attack body's own tissues c.Autoimmune diseases like arthritis have inflammation without infection

8 Major Histocompatibility Complex
The basis of “self” Genes for cell surface glycoproteins In humans: human leukocyte antigens (HLA) ENORMOUS variation (polymorphic) 2 Types: Class 1: found on all nucleated cells Class 2 : found on macrophages, B cells, CD4 T cells


10 Phagocytic and Natural Killer Cells
Neutrophils: Most abundant WBC’s Chemotaxic Engulf invaders, then self-destruct Monocytes: Less abundant, but more effective than neutrophils Form macrophages Reach pathogen with pseudopodia Engulf pathogen, fuse it with a lysosome Kill pathogen with toxic oxygen or enzymes Phagocytosis = engulfing invaders; nonspecific Chemotaxic = cells damaged by microbes release chemical signals, neutrophils travel to the site of damage Macrophages live longer than neutrophils Toxic oxygen = superoxide anion Problem: bacteria that pseudopodia can’t grab


12 More WBC’s Eosinophils:
Fight large invaders (ex: parasites) Natural Killer (NK) cells: destroy “self” cells infected with viruses, cancer cells


14 The Inflammatory Response
Histamine is released by circulating leucocytes called basophils and by mast cells in connective tissue. Histamine triggers both dilation and increased permeability of nearby capillaries. Also discharge prostaglandins and other substances that promote blood flow to the site of injury. Greater clotting capacity, faster repair Initiated by chemical signals From microbe- Chemotactic factor From damaged ‘self’ cells (ex: histamine) Chemokines from damaged cells attract phagocytes Pus = dead phagocytes + fluids Extreme = septic shock Mech of increased blood flow: precapillary sphincters dilate, postcapillary sphincters constrict Phagocytosis: most important part of inflammation Septic shock: extreme, widespread infection,  WBC production, fever,  BP *Most common cause of death in CCU’s

15 The Complement System Antimicrobial proteins ~ 20 serum proteins
Function: microbe lysis Interferons: 1 activates phagocytes can be made by recombinant DNA


17 Another set of proteins that provide nonspecific defenses are the interferons, which are secreted by virus-infected cells. While they do not seem to benefit the infected cell, these proteins diffuse to neighboring cells and induce them to produce other chemicals that inhibit viral reproduction. Interferon limits cell-to-cell spread of viruses, helping to control viral infection. Because they are nonspecific, interferons produced in response to one virus may confer short-term resistance to unrelated viruses. One type of interferon activates phagocytes.

18 Temperature Response Pyrogens
Ex: Interleukin-1 Detected in blood by hypothalamus -- raise in body temp How it works: Speeds cellular reactions Stimulates phagocytosis Stimulates liver/spleen to store Fe Endotherms - may regulate behaviorally


20 Immunity terms Humoral vs Cell mediated Acquired/active vs Passive
Lymphocytes: T and B cells, specific Antigen: Foreign molecule (from pathogens, pollen, transplanted tissue, etc.) Antibodies: made by B cells, specific Antigen receptors: on membranes of T & B cells B cells: membrane antibodies T cells: similar, but never secreted T & B begin developing in bone marrow T finish in thymus B finish in bone marrow (but actually named after bursa) Pathogen: disease causing agent

21 T cells TI = inducer TC = cytotoxic TH = helpers TS = suppressor
killers TH = helpers Activate others TS = suppressor Causes B cells to ignore antigens

22 Antigen presentation Antigen binds to MHC within cell
MHC molecules bring proteins to surface



25 Cell mediated response
TC cells kill cancer cells, viral infected cells All cells have class 1 MHCs (all susceptible to viral infection) Class 1 MHC captures viral protein MHC + antigen move to cell surface Present to T cytotoxic cell Enhanced by CD8 Active killer cell


27 Mechanism T cytotoxic cell releases perforin
Forms pores in membrane of target cell Cell lyses, pathogen inside is exposed to circulating antibodies T cytotoxic cell moves on to other cells infected w/ same pathogen Tumor cells have ‘tumor antigens’ Some cancers, epstein-barr virus:  class 1 MHC moleucles, escape defense




31 Antibody mediated immunity
Aka Humoral immunity, B cells activated, antibody production Ex: macrophage engulfs a bacterium Class 2 MHC picks up bacterial peptide MHC + antigen move to cell surface Presents to T helper cell/releases Il-1 Enhanced by CD4 receptor on T helper cell T cell proliferates Activated T helper cells: secrete cytokines to stimulate other lymphocytes Cytokines: ex = IL-2 helps activate B cells become plasma cells activates cytotoxic T cells

32 Humoral response in detail
B cell activation by IL-2, proliferate into plasma and memory cells Plasma cells: secrete antibodies Memory cells: long-lived Some antigens are T-independent Bind to membrane antibodies on B cells Plasma cells made w/ out signal from T cells Q: which cells secrete IL-2 to activate the B cells? A: helper T




36 Structure of antibodies
Globular protein, in plasma, aka: immunoglobulins (Igs) Structure: 4 chains: 2 heavy, 2 light Constant region Variable region Epitope: part of the antigen where antibody binds 5 classes Made in vitro Polyclonal: made from many B cell clones Work on different epitopes of the same antigen Monoclonal: made from one B cell clone All work at the same epitope of the same antigen



39 How antibodies work Neutralization: Opsonization: Agglutination:
Block antigen activity Opsonization: Enhance macrophage attachment/phagocytosis Agglutination: Clumping Complement fixation: can be activated by antibodies or by pathogens Antibodies attach to antigens Complement proteins activate, cause lysis Ex of neutralization: attach to the molecules on a virus that the virus needs to attach to the host cell Agglutination: neutralizes & opsonizes

40 Active vs. Passive Immunity
Active immunity: your own response Natural: from infection Artificial: from vaccinations Passive: antibodies from another individual Ex: across placenta, through breast milk Ex: antivenoms,Rhogam Rhogam: injection given to Rh- mothers after birth of Rh+ child. Destroy fetal cells before her immune system responds to them, develops antibodies Anti Rh antibodies are class IgG - can cross placenta Rhogam: injection given to Rh- mothers after birth of Rh+ child. Destroy fetal cells before her immune system responds to them, develops antibodies Anti Rh antibodies are class IgG - can cross placenta Anti A, Anti B are class are IgM - can’t cross

41 Tissue transplantation
Blood types: ‘A’ and ‘B’ antigens T-independent humoral response Antibodies don’t cross the placenta Organ transplants Rejection due to MHCs that are too dissimilar Suppress immune system to decrease rejection Bone marrow: graft rejection

42 Overactive/under active Immune Systems
Allergies: antigen induces inflammatory response Histamine released from mast cells Anaphylactic shock: severe allergic reaction, may cause death (due to  BP) Epinephrine may counteract Autoimmune diseases: immune system attacks self tissue Lupus, rheumatoid arthritis, MS, type 1 diabetes Lupus: autoantibodies against histones, DNA, etc. R. arthritis: joint bones/carilege MS: myelin Type 1 diabetes: beta cells in pancreas (insulin dependent)

43 Under active Immune System
Immunodeficiency diseases: Severe combine immunodeficiency (SCID) Genetic, need marrow transplant May treat w/ gene therapy Hodgkin’s: damages lymphatic system AIDS Susceptible to opportunistic infections Caused by HIV, 2 strains Infect CD4 cells: requires CD4 receptor and co-receptor Implications for treatment: Chemokines bind to coreceptor - may block entry Defective CD4 receptors prevent infection

44 More on AIDS High mutation rate Test is actually for HIV antibodies
T cell count indicates disease progression Drugs only slow the progression, are very expensive 30-40 million (?) world wide cases 70% in sub-saharan Africa

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