Immune team

Cell injury can result from : Hypoxia Hypoxia Physical & chemical agents. Physical & chemical agents. Microbial agents. (defective immunity). Microbial agents. (defective immunity). Immune reactions. (abnormal responses) Immune reactions. (abnormal responses) Genetic factors. Genetic factors. Nutritional imbalances. Nutritional imbalances. These Various stimuli cause cell injury & induce a complex vascular & cellular response called : Inflammation

Inflammation

There are 2 types of infections : - 1 – sub clinical infections (MCQ) : we have it all the time so it is common, it have no symptoms or signs because it get controled before produce symptoms 2 – clinical infections : they are quite rare, they produce symptoms and usually indicate failure to control infections All defense mechanisms are collectively called immunity Immunity is divided into :(MCQ) Natural ( innate ) : is non-specific Adaptive ( acquired ) : Specific 1 – the to divisions are well integrated 2 – the 2 division are connected through a cytokine network ( inflammatory pathway )

The immune system has to main functions : Recoginition 1- the immune system is able to recognize and distinguish one pathogen from another through chemical differences 2- and able to discriminate between foreign molecules and the body own cells Response The response is divided to : Effector response : this mechanism usually accure in natural immunity, once a foreign body has been recognized, the immune system will call and recrutis all his warriors army ( effecror cells ) to defeat that organism Memory response : this mechanism usually accure in acquired immunity, later exposure to the same foreign body induce a response that call and recrutis a special unit of the big army ( maybe Marine ) that have an effecte on that organism, so this mechanism is specific and contain memory for different pathogens

Differences between the natural and acquired immunity Natural immunity acquired immunity Very limited diverse cell surface Cell surface receptors receptors (Fewer than 100 receptor) Non specific specific No memory retention there is immunologic Because the cells half memory Life is short Mechanism of recognition of microb Effecror mechanism ( response ) Immunologic memory

Natural immunity serve as : A critical early defense, ( mobilized within minutes after invasion by microbes ) A warning signal that a microbe is invading the tissues Stimulate & influence adaptive immunity ( secrete cytokines & activate cells ) A progressing infection that pass natural defense mechanisms will be stoped by adaptive ( antibody mediated response called humoral immunity ) if it was extracellular infection, but if it was intracellular infection it will be stoped by adaptive ( cell mediated response called cell mediated immunity )

Defense mechanisms of natural immunity : - ♥ anatomic barriers ♥ 1- skin : is a mechanical barrier that work as a shaled preventing microbes from entering It has an acidic enviroment that retards grouth of microbes 2- The mucus membranes : Normal flora compete ( fight ) with microbes for attachment sites and nutrients 3- Mucus secreted by goblet cells entraps foreign bodies & microbes 4- Cilia propel microorganisms out of the body by coughing and sneezing ( smooking cause damage to cilia so smookers are expoused to lung infections ) disruptions of anatomic barriers : 1- burns, cut wounds, skin diseases (eczema) 2- Aseptic techniques ( taking a blood sample or I / V catheters ) 3- Disruption of the mucus membrane ( oral cavity ) by dental procedures

Physiologic barrier ♥ ♥ Temperature: Normal body temperature inhibits growth of some pathogens ( fever inhibits growth of pathogens) Low pH Acidity : of stomach contents kills most ingested microbes Chemical mediators : Lysozyme cleaves bacterial cell wall, and Collectins wich stick to the pathogen so it get phagocytosed Natural antibiotics : like defensins, cryptidins in stomach Physiologic functions : Coughing, sneezing, voiding urine, tears, saliva in oral cavity etc when Physiologic functions are absent like in ( Inability to cough or Urine retention ) predispose to infections is likely to be

Circulating effector cells 1- Neutrophils ( most important ) 2- Macrophages 3- Natural killer (NK) cells (viral immunity) 4- Eosinophils (parasitic and allergic immunity) 5- Mast cells (mediator of inflammation ) 6- Platelets ( coagulation and mediator of inflammation) 7- B-1 cells found in fetus & neonates respond to bacterial antigens ( polyssacharides ) The Phagocytic cells have two hands on its surface that use them to shake the two hands found on pathogen surface so it can recognize it The first hand of Phagocytic cells called Toll - like receptor (TLRs) that shake lipopolysaccaride (LPS) hand found on pathogen surface (gram negative bacteria ) The second hand of Phagocytic cells called Pattern-recognition receptors (PRR) that shake Pathogen - associated molecular patterns hand (PAMPs ) found on pathogen

Neutrophils : Mediate the early phase of inflammation They are recruited to the site of infections by a process called chemotaxis comprise ( percent) Of the WBC Short - lived cells work in extra - cellular infections Contain enzymes Perform killing by : 1- Oxygen - dependent mechanisms 2- Oxygen - independent mechanisms It is a polymorphonuclear cell

Chemotaxis of phagocytic cells involve the following steps : 1- Rolling ( loose adherence ) to endothelium 2- Activation of cells 3- Stable adherence to endothelium 4- Transmigration into tissue spaces

Mononuclear cells Monocytes & Macrophages Long - lived cells Contain enzymes & secrete many cytokines work in intra-cellular infections Professional phagocytic cells Antigen – presenting cells important in both natural & adaptive immunity Circulating monocytes enter tissues & become resident macrophages, e.g of tissues: 1- Sub - epithelial connective tissue 2- Interstitia of organs 3- Vascular sinusoids of the liver & spleen 4- Lymph nodes

Macrophages are activated by Bacterial products. LPS. (gram neg. bacteria) Bacterial DNA Secrete cytokines, attract neutrophils Induce local inflammation. Macrophages are strategically located at sites where Microbes enter the tissues They recognize microbes first by their receptors (PRR ) Become activated,secrete cytokines and attract Neutrophils

Macrophages produce many cytokines : Act on various tissues & cells. 1. IL IL TNF 2. TNF 3. IL-6 3. IL-6 4. IL-8 4. IL-8 5. IL IL-12

macrophges perform multiple functions : 1. Induce local inflammation. 2. Perform phagocytosis. 2. Perform phagocytosis. 3. Activate coagulation. 3. Activate coagulation. 4. Enhance antigen presentation. 4. Enhance antigen presentation. 5. Initiate tissue repair. 5. Initiate tissue repair.

Macrophage Th cell Macrophage Cytokines Lymphokines Cytokines Anti-microbial functions Anti-tumor function Activate Invading agentAntigen presentationActivated macrophage Functions of macrophages :

Mechanism of intracellular killing by phagocytic cells 1- Lysosomal enzymes 2- Production of reactive oxygen intermediates 3- Production of nitric oxide 4- circulating effecter proteins

Natural killer cells A class of larg granular cytotoxic lymphocytes that do not have T or B cell receptors They are antibody – independent killers of tumors cells and also participate in antibody – dependent cell mediated cytotoxicity NK-cells are activated by : IL-12 and IL-15 Which are Produced by macrophages Functions of NK cell : 1- anti - viral activity 2- anti – tumor activity

Circulating effector proteins : 1 - The complement proteins 2 - Mannose- binding lectin 3 - C – reactive proteins 4 - Coagulation factors 5 - Cytokines

The complement system is a biochemical cascad that’s help to clear pathogens from the body it consists of a number of small proteins found in the blood and synthesized by the liver Normaly they are inactive [ zymogens ] Activation of the complement system lead to initiation of important effects which include : 1- Release of chemotactic factors (C3a and C5a ) 2- Opsonisation of microbes (C3b ) 3- Lysis of target cells (C8 & C9 ) The complement proteins

The complement system is activated by 3 pathways : 1 - classical pathway, require antigen - antibody interaction 2 - alternative pathway, activated by bacterial products (LPS,DNA ) 3 - lectin pathway, activated by mannan-binding lectin

C5 b C6 C7 C9C9 C8 C9C9 C9C9 CC C9C9 C9C9 MEMBRANE ATTACK COMPLEX

Cytokines of natural immunity 1- interferons ( anti - viral ) 2 – IL-1, TNF and Chemokines ( mediate inflamation ) 3 – IL-12 and IL-15 ( NK – cells ) 4 – interferon – gamma ( act on macrophages ) 5 – IL-6 ( act on bone marrow ) 6 – IL-10 and TGF-B ( limit local inflammation )

Other functions of Cytokines The Cytokines IL-1 and IL-6 and TNF-alpha coordinate body responses to infections by acting on : 1 – liver, they induce the synthesis of acute phase proteins 2 – bone marrow, by stimulating the mobilization of neutrophils 3 – Hypothalamus, they induce it to increase body temperature (induce fever ) 4 - Fat & muscle, to supply proteins & energy 5 - T and B Lymphocytes, to become activated and produce adaptive immune responses

Summary. 1. Natural Immunity is the first line of defense. of defense. 2. It influence & stimulate subsequent 2. It influence & stimulate subsequent adaptive immune responses. adaptive immune responses. 3. The immune response is a : 3. The immune response is a : * Protective. * Protective. * Sub clinical. * Sub clinical. * Localized reaction * Localized reaction

5 - All are fearures of NK cells EXCEPT : a)phagocytic. b)anti-tumor activity. c)stimulated by activity. c)stimulated by IL-12. d)activated by interferons. e)anti-viral activity

6 - Regarding cytokines all of the following are true EXCEPT : a) they are low MW proteins. b) they act with surface receptors. c) are long acting mediators. d) regulate inflammation

7 - Regarding CD molecules : a) CD3 is found on all B calls,not T cells. b) CD1 is found on mature T cells. c) CD19+CD20 are found on T cells. d) CD4 is called cytotoxic. e) CD56 found on NK cells

8 - All are features of complement system EXCEPT : a) lysis of damaged cells. b) opsonization of microbes. c) chemoattractants for neutrophils. d) participates in inflammation. e) inhibits cytokines