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The Basics of Immunology Presentation (Updated)
The Basics of Immunology Presentation (Updated)
The Basics of Immunology Presentation (Updated)
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The major elements of the innate and adaptive immune systems Adaptive immune Innate immune system Character/ system element * Resistance not improved by Action repeated infection * acts as the first line of defense against infection. Soluble factors or mediator s Cells
Antibody, Lymphocyte Lysozyme, complement, acute derived cytokines phase proteins e.g. CRP, Macrophage-derived cytokines, e.g.-, - and -interferons, tumor necrosis factor lymphocytes Phagocytes (neutrophil polymorphs, monocytes and macrophages) Natural killer (NK) cells
Cutaneous and mucous Skin, mucous membranes immune systems, antibody in mucosal
Physiochemical barriers
Innate Immunity
Click to edit Master subtitle style
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defence mechanisms are: i- Always present (prior to exposure to infectious microbes) ii- Ready to recognize and eliminate microbes iii- Defense mechanisms include physical barriers, phagocytic cells, eosinophils in the blood and tissues, natural killer cells and various bloodborne molecules.
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Mechanical 2. Chemical 3. Biological .Humoral 1. Complement .Cellular 1. Neutrophils 2. Macrophages 3. Phagocytosis 4. NK cells
1.
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Anatomical
Mechanical 2. Chemical 3. Biological .Humoral 1. Complement .Cellular 1. Neutrophils 2. Macrophages 3. Phagocytosis 4. NK cells
1.
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Anatomical- Mechanical
Skin-
squamous epithelium. It is both a PHYSICAL barrier and desquamation Mucous membranes e.g. peristalsis in GI tract, mucociliary escalator in the respiratory tract
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Anatomical-Chemical
Sweat
glands in the skin, associated with the hair follicles. Produce sebum (oily secretion)= consist of lactic acid and fatty acids, PH 3-5, that inhibits growth of microorganisms. Tears- lysozyme HCl- stomach acid Saliva Defensins Surfactant
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Sebaceous
Anatomical
Mechanical 2. Chemical 3. Biological .Humoral 1. Complement .Cellular 1. Neutrophils 2. Macrophages 3. Phagocytosis 4. NK cells
1.
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Anatomical-Biological
Normal
flora competes with pathogenic flora for nutrients and colonisation e.g. Straph aureus, Strep. epidermidis. Etc.
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Anatomical
Mechanical 2. Chemical 3. Biological .Humoral 1. Complement .Cellular 1. Neutrophils 2. Macrophages 3. Phagocytosis 4. NK cells
1.
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Complement
Complement
can be tricky to understand Everybody panics about complement, but theres no need to! Unless you are studying immunology in depth, there is no need to know the intricate details of all the pathways. The handouts explains the details of complement. The next slide is all you need to know for complement.
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Complement is a cascade system of many proteins that has many roles including: Opsonisation (enhances phagocytosis) Clearance of immune complexes Clearance of apoptotic cells Regulation of antibody responses It has 3 pathways- called the Classical, Lectin and Alternative Pathway. Ultimately, all the pathways lead to the formation of a membrane attack complex (MAC) which punches a hole in the pathogen cell wall, causing lysis. In addition to MAC, complement causes release of byproducts which can act as opsonins and help clear antigen-antibody complexes.
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Complement Cookbook!
In
the handout Ive described the three pathways using the analogy of recipes to help you learn! Classical Pathway recipe- doing it the old fashioned way Alternative Pathway recipe- the cop out Lectin Pathway- exotic recipe! Look at the notes to understand more about the intricate details of the complement system!
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Method:
1.
2.
3.
4.
Add some C1 complex into the hot pan (bacterial cell wall). This will cause the complex to become activated. Then throw in some C4 with the C1. The C1 will cleave the C4 into C4a, C4b. Remove the C4a from the pan and discard. Notice that the C4b will bind to the wall. Chuck in some C2 now. C1 will also cleave C2 into C2a and C2b. Remove the C2b from the mixture and discard. Notice that C2a will bind to the C4b. You have now made C3 convertase, an enzyme! However, we're not done cooking just yet. Add in some C3 to complete the 4/20/12
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For
advanced chefs! To make this dish into a michelin star masterpiece follow the recipe for Lytic Attack Pathway! Don't waste the C2b and the C3a and C4a, these can be used to make opsonins, chemoattractants and prokinin. If you find you've put in too much C1 into the recipe, don't panic! C1INH can be added to inhibit C1.
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Note!
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METHOD:
some C3 into the pan with water. The C3 will form C3a and C3b. Add in some factor B which binds the C3b. Add in some more C3, which will cleave into C3b and a. The C3bBC3b is now C5 covertase! You have now successfully made C5 convertase! Add Factor P to taste! For advanced chefs! To make this dish into a michelin star masterpiece follow the recipe for
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Chuck
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METHOD:
Add
in some MBL, ensure this sticks to the mannose on the surface. Add in some MASP1 and MASP2. Ensure they stick on to the MBL. This now acts just like C1 of the classical pathway. Add in C4 and watch the MASP1/2/MBL complex cleave it into C4b which sticks to the pan and C4a which you can discard from the pan. Add in C2 and watch it be cleaved into C2a and C2b (which you can discard). C2a sticks to C4b. Add in C3 which gets cleaved into C3a 4/20/12 (discard) and C3b which can bind to C4b
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The Products of Complement have important function mnemonic roles- of C3a Complement:
versus C3b C3a: Activates Acute [inflammation].C3b:Bonds Bacteria [to macrophages--easier digestion]. If wish to know more than just C3:C3a, C4a, C5a activate acute.C3b, C4b bind bacteria.
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So in Summary.
C- Cascade O- Opsonisation e.g. C3a, C2b M- MAC P- Phagocytosis L- Lysis of pathogens results E- Enzymes cleave components to form the cascade M- Mannose binding lectin, alternative and classical pathways E- Everything is regulated tightly e.g. DAF, factor B, factor P N- Non specific to pathogen/No memory i.e. INNATE
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Anatomical
Mechanical 2. Chemical 3. Biological .Humoral 1. Complement .Cellular 1. Neutrophils 2. Macrophages 3. Phagocytosis 4. NK cells
1.
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in tissues include alveolar macrophages, splenic and lymph nodes resident and recirculating macrophages. Resident macrophages are found in the connective tissues and in every organ in the 4/20/12 body.
The
two types of circulating phagocytes, neutrophils and monocytes when recruited to sites of infection, they recognize and ingest microbes for intracellular killing
Neutrophils
(also called the polymorphonuclear leukocytes, PMNs) are the most abundant leukocytes in the blood, numbering 4000 to 10,000 per mm3. Monocytes are less abundant than neutrophils, numbering 500 to 1000 per mm3 of blood
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Mnemonic to remember
Never Let Monkeys Eat Bananas Neutrophils (most common) Lymphocytes Monocytes Eosinophils Basophils (least common)
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Neutrophils
Characteristic Nucleus Cytoplasm has granules Primary granules: contain lyzozyme, defensins, MPO, elastase cationic proteins Secondary granules: contain lysozyme, NADPH oxidase, lactoferrin
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Macrophages
are similar, but contain less granules and a kidney shaped nucleus.
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PHAGOCYTOSIS
Phagocyte
Response to Infection:
THE SOS Signals These molecules send an SOS signal to the phagocyte to alert them of an infection. These are: 1. N-formyl methionine containing peptides 2. Clotting system peptides 3. Complement products 4. Cytokines
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Phagocyte Response
Phagocyte
Response Once the phagocyte has been alerted, the phagocyte responds by: 1. Vascular adherence: it sticks to the endothelial cells via adhesion molecules such as P selectin and E-selectin. 2. Diapedesis: phagocyte moves in between the endothelial cells 3. Chemotaxis: substances sent from the infected tissue (chemoattractants) attract the phagocyte into the tissue. 4. Activation: the phagocyte becomes
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Granule/lysosome Phagolysosome
formation
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NK cells
NK
cells are responsible for the non specific killing of virus infected and malignant cells. You dont need to know much more than this, however, the details of their activation and function are in the handout.
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Imagine a small town (body) being attacked by forces from outside (pathogens). The first line of defence for this town is the giant wall they have built around it. This immediately is a barrier for an any army attacking them. This huge wall represents the skin. From the top of the wall, the defenders of the town can throw buckets of acid and boiling water at the soldiers below them. This represents the HCl stomach acid and tears and saliva that contain antimicrobial substances used to destroy the pathogens and also by complement products. At the same time, the inhabitants of this town are very clever, they employ soldiers masquerading as enemy soldiers and use them to infiltrate the enemy and steal their guns and armour from them. This represents the normal flora which competes with the pathogen for nutrients and colonisation. The enemy is too strong and the battle continues ferociously. The inhabitants of the town are keen to keep the enemy soldiers outside and stop them infiltrating the wall. They use more force. They decide to fire through panels in the wall, cannon shots at the enemy to break up their ranks (phagocytes). Fighting continues and the enemy are closer and closer to the wall, eventually they manage to break down the wooden door and infiltrate the town. What will the inhabitants do now? Acquired Immunity!
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What
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Antigen processing
Presents antigen to:
Intracellular pathogens (i.e. Viruses) CD8 killer T cell
E pa x t r ( i . th a c e. o el Ba gen lula ct s r er ia )
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