Immunology Study Guide PDF

-​ Examples: -​ Psoriasin Lecture 01: Module introduction -​ Small proteins 3 lines of defence...

-​ Examples: -​ Psoriasin Lecture 01: Module introduction -​ Small proteins 3 lines of defence -​ Produced and secreted by 1.​ Physical and chemical barriers [continuous] keratinocytes a.​ Skin blocks pathogens -​ Prod local when bacteria detected b.​ Mucous membranes - nose/throat/intestines -​ Mode of action : 2.​ Innate immunity - rapid and nonspecific [rapid] -​ Membrane Disruption: a.​ Macrophages, NK cells and dendritic cells destabilises and damages 3.​ Acquired immunity - slow, long lasting and highly specific bacterial membranes, >> bacterial a.​ Lymphocytes B cells and T cells cell death, -​ Zinc Sequestration: binds to zinc, First line of defence depriving bacteria of essential -​ Physical nutrient >> inhibiting growth and -​ Skin: Pathogens bypass mucous membranes survival. -​ Epidemics - packed epithelial cells, outer later -​ Target Specificity: effective contain dead keratinocytes against Gram-negative bacteria, -​ Dermis - packed with immune cels demonstrating selectivity in its -​ Effective bacteria (unsuitable for microbes): antimicrobial activity. -​ pH: slightly acidic -​ Maintains Skin Barrier: -​ High concentration of NaCl eliminating harmful pathogens -​ Often dry (due to constant cleaning) while preserving beneficial -​ Has AMPs microbes, maintaining the skin’s -​ Varies temperature defense and homeostasis -​ Constant shedding -​ Defensins: -​ Thick later dead cells -​ + charged peptides (30-45AA) -​ Has immune cells -​ 2 types: alpha defensive (in immune -​ Epithelial lining: barrier, signals presence pathogen cells) & beta defensins (eg skin and -​ mucous and cillia: thick and constant to trap bacteria saliva) -​ Normal microflora -​ Kills bacteria and viruss - e.coli, -​ Coughing, sneezing and vomiting (expulsive reflexes streptococcus and pseudomonas -​ Chemical -​ Makes pores to break membrane and -​ pH: high in stomach; high salt and pH in skin depolarise -​ Saliva: -​ Local conc can be big -​ Lysozymes (an enzyme) -​ Lactoferricin -​ Target cells (xx peptidoglycan >> cleaves -​ In saliva and breast milk glycosidic bonds between NAG & NAM >> -​ Chelates iron Weakened cells wall >> susceptible to osmotic -​ Antimicorbial pressure) -​ Cleaved by enzymes (eg -​ Cleaves sugar back bones pepsin/trypsin) intro AMP lactoferricin -​ Bursting of cells wall (cells lysis as succumbing to osmotic pressure) -​ AMPs (antimicrobial peptides) [found skin and saliva and siderophores -​ Catioininc and hydrophobic -​ Xx bacteria, viruses and fung -​ Mode of actions -​ Target - charged bacterial membran/cell walls -​ Eukaryotes has lower charge - no affected by AMPS Lecture 02: The innate immune system -​ Lipotechoic acid: G+ cell wall​ 3.4..1.​ Hydrolytic enzymes (e.g., Phagocytosis: proteases, lipases) degrade -​ Carried out by: -​ Carbohydrate: microbial components. -​ Macrophages - resident in the tissues -​ Mannan: fungi & bacterial cell wall 3.4..2.​ Reactive oxygen species (ROS) -​ Neutrophil - recruited from the blood -​ Glucans: fungal cell wall and nitrogen intermediates, toxic -​ Steps in the phagocytosis -​ Peptidoglycan: bacterial cell wall to microbes and contribute to 1.​ Chemotaxies - attractions Opsonization: their killing. 2.​ Attachment by receptor binding -​ Process where pathogens or particles are coated with 3.5.​ Microbial Killing and Digestion: 3.​ Ingestion and phagosome formation opsonins, such as antibodies or complement proteins, ​ Inside the phagolysosome, the acidic 4.​ Lysosome fusion -​ enhance their recognition and uptake by phagocytes environment, lysosomal enzymes, and 5.​ Microbial killing and diggestion -​ facilitates efficient phagocytosis ROS kill the ingested microbe and break it 6.​ Release of waste -​ helps the immune system eliminate harmful invaders. down into small, non-harmful components.​ -​ Recognising microorganisms -​ Steps 1.​ Tagging: Antibodies coat the pathogen, marking it 3.6.​ Debris Clearance: -​ PAMPS are recognised by PRRs for destruction. ​ either released as waste or processed for -​ Macrophages: Pattern Recognition Receptors [PRRs] 2.​ Recognition: Macrophages "see" the antibody's Fc antigen presentation, linking the innate and -​ Detection of fungi/bacteria region using their Fc receptors. adaptive immune responses. -​ Toll-like receptors (TLRs) 3.​ Engulfing: The macrophage binds to the antibody How macrophages might kill bacteria -​ 13 different types and "eats" the pathogen. -​ Acidification: reduction of pH 3.5-4 by inserting H+ -​ Different TLRs recognise PAM 4.​ Killing: The pathogen is destroyed inside the ATPase Pump -​ Types of TLRs {remember at least 3] macrophage. -​ ROS species: Hypochlorite OCL- (containing bleach), -​ TLR2 The process of phagocytosis and cell killing nitric oxide, superoxise and peroxynitrie [HNSP) -​ Ligand: Peptidoglycan 1.​ Recognition: PAMPs and PRRs -​ AMP: defensincem cationic peptides for ion pores in -​ Location: bacterial cell wall component 1.1.​ PAMPS on microbe surface membrane -​ TLR4 1.2.​ PRRS on immune cell surface -​ Enzymes: lysozomes degrades peptidoglycan layer of -​ Ligand: lipopolysaccharide (LPS) 1.3.​ It will bind and clutches the receptors gram +ve bacteria Dases, RNses and Proteases -​ Location: Bacterial cell wall component 2.​ Ingestion and phagosome formation -​ Nutrient removal: siderophore and nutrient tranportes -​ TLR5: 2.1.​ Receptor initiates phagocytosis via signal Cell signalling and immune gene expression -​ Ligand: flagellin transduction -​ Upon binding: -​ Location: bacterial appendage 2.2.​ Actin arrangement pushes membrane around -​ TLRs combine -​ TLR7 target cell (pseudopdia) -​ TIR domain signals to the cell to express immune -​ Ligand: ssRNA 2.3.​ Phagosome: large endosome formed genes -​ Location: Viruses (influenza,HIV-2) 3.​ Phagosome maturation -​ SIgnal transduction enfs on NF-kB - main shared -​ TLR9 3.1.​ Formation of the Phagosome: transcription factor -​ Ligand: dsDNA ​ tmicrobe is engulfed into phagosome -​ NF-KB -​ Location: bacteria & herpes simplex inside the phagocyte. -​ AMPS: promotes AMP production to kill microbes virus 3.2.​ Fusion with Early Endosomes: -​ Phagosomal proteins: enhance phagocyte capacity -​ TLR10 -​ Ligand: pili ​ interacts with early endosomes, deliver to kill by upregulating protein involved in -​ Location: bacteria proteins that initiate the maturation process. phagosome maturation and microbial degradation -​ Microbes: Pathogen Associated Molecular Pattern ​ proteins help recruit signaling molecules -​ Cytokines: induce production of cytokines to recruit [PAMPS] and enzymes. and activate immune cells -​ Not easily mutated: 3.3.​ Fusion with Late Endosomes: -​ Inflammatory proteins: control expression mediators -​ Types: ​ further fuses with late endosomes, that amplify inflammatory response -​ Nucleic acid: ddRNA and ssRNA in viruses ​ environment begins to acidify due to the -​ Inflammatory Proteins: NF-κB controls the -​ Proteins: activity of proton pumps (v-ATPases). expression of mediators that amplify the -​ Flagellin: Bacterial flagella of cell wall ​ pH decreases, creating hostile inflammatory response -​ Pilin: bacterial pilli of cell wall environment for the microbe -​ Lipids: 3.4.​ Fusion with Lysosomes: -​ Lipopolysaccharide (LPS): G- cell wall ​ phagosome fuses with lysosomes, forming a phagolysosome. Lysosomes contribute: Lecture 03: The inflammatory Response b.​ Damaged cells releases chemokines/cytokines​ ​ The Inflammatory response basic: -​ Cascade complex at the site of infection 4.​ Capillary alteration - vasodilation Inflammatory mediators: Cytokines -​ Redness/edme, swelling, pain and heat [4 cardinal signs] a.​ Vasoactive > mast cells release histamine in -​ Leukocyte uses cytokines to communicate -​ Mass recruiting of immune cells response to tissue damage -​ Cytokines uses cytokine receptors -​ Acute [ short term ] infection in respons to infection b.​ Vasodilation > capillaries and venules inc diameres -​ Main functions -​ Chronic [ long term ] response to cell damage (eg - IBS c.​ Capillaries becoming permeable (swellig/edema)​ -​ Change cell adhesiveness and arthritis) (b and c - cytokines release a message that cells -​ Affect enzyme activity -​ Types of cells have to exit hence vasodilation helps leak immune -​ Determine when cells dies or survives -​ Neutrophils cells out) -​ Alteration of gene expression -​ Polymorphonuclear (round cells with lobed nucleus d.​ Blood vol increase, flow vel slows down -​ Communication steps -​ Most abundant e.​ Inflammatory mediators esc into blood 1.​ Inducing stimulus -​ Circulate in blood (dies after 8h) f.​ Fluid and plasma proteins enters tissue 2.​ Cytokine gene activation [cytokine-producing cell] 5.​ Extravasation - Attraction of neutrophils then monocytes 3.​ Cytokine secretion -​ Phagocytes (not in the slides) -​ Macrophages (Cooper cells) a.​ 1. Rolling 4.​ Reaching cytokine receptor -​ Resident cells: !st to encounter microbes i.​ Endothelial cells are activated [en TNF] to 5.​ Signals -​ Phagocytes express cell adhesion molecules [eg selectin] 6.​ gene/enzyme activation [target cells -​ Found in external barriers on luminal surface hence making them sticky 7.​ Biological effect [eg proliferation/differentitation/cell -​ Gastrointestinal submusocal later ii.​ Selection bind to sugar neutrophil surface death] -​ Skin molecule -​ Cytokine family -​ Alveoli of lung iii.​ Leukocyte attach weakly and tolls -​ Acts on cytokine receptors -​ Monocyte recruited to site to differentiate b.​ 2. Activation -​ Types of eg: IL-1, IL-8, TNF and Interferons -​ Dendritic cells i.​ Cytokines [TNF and IL-1] cause endothelial to -​ IL-1 -​ Resident in tissue express ICAMS -​ Release by macrophages and epithelial cells -​ Sense danger and release cytokines ii.​ Chemokines cause leukocytes to express high -​ Binds to IL-1 receptor -​ Mast Cells affinity integrin​ -​ Proinflammatory -​ Resident in skin and mucosal tissues [ integrin: ICAM interaction is very strong; -​ TNF -​ Activated by: PAMPS, cytokines or antibodies clusters in the membrane increasing avidity of -​ Release by macrophages and neutrophils -​ Release histamine and cytokines >> vasodlation, inc leukocyte] -​ Binds to TNF receptor capillar permeability and stimulation of inflammation c.​ 3. Arrest: leukocyte stops and adhere strongly to -​ Proinflammatory via cytokines endothelial cells then start to spread -​ IL-8 [CXCL8) -​ Linked to allergic reaction [ histamine cause d.​ 4. Diapedesis -​ Recuitrs and activats neutrophils inflammation to allergen s i.​ Junctions of endothelial cells are broken -​ Chemokines - chemoattractants - affect mobilization of ​ ii.​ Leukocytes crosses into tissues cells ​ iii.​ Chemoattractant > chemokines indicate site -​ Subgroup of cytokines Inflammatory response steps: infection -​ Small and structurally related -​ Before infection/injury 6.​ Phagocytosis and would clearance -​ Cause effect of cell adhesiveness -​ Monocytes and neutrophils circulates around the body a.​ Neutrophils: 1st response -​ Affecting cell moment -​ Resident macrophages, dendritic cells and mast cells b.​ Monocytes (turns into macrophages) provide -​ Chemoattraction waits in the tissue protection -​ Est concentration graduated 1.​ Injury/infection c.​ DC/macrophages: travels to lympnodes to present -​ Released on early infection by macrophages a.​ Localised tissue damage/instant pain antigens and damaged cells b.​ Bacterial entry 7.​ Clotting ​ -​ Named by conserve cysteine C residue: 2 main 2.​ Activation of immune cells (PRR/PAMPS) ​ -​ CC [ 2 adjacent CC residues in amino terminus] a.​ Innate immune cells activated > activated via ​ -​ Attracts monocyte and macrophages PRR/PAMPS ​ -​ CXC [CC separact by an amino acid] 3.​ Cytokine release -​ Attracts neutrophils a.​ Release of cytokines, chemokines, histamine and ​ bioactive lipids (TNF, IL-8, IL-1) ​ ​ ​  4.​ Bb >> C3(H2O)Bb [initial C3 convertase) -​ pro-infllamatory - attracts and activate leukocytes and 5.​ [another pathway] initial convertase with C3 acts on capillaries Lecture 04: The Complement System 6.​ High reactive C3 and Cb Basics: 7.​ Factor B binds with C3b Why doesn’t complement kill our own cells? -​ Part of the innate system 8.​ Factor D cleave Factor B in the C3bB complex -​ Having receptors that inhibit complement cascade -​ Found in the blood plasma into two fragments: -​ Eg: CD59 on mammalian cells > inhibiting C5b-C8 -​ Produced in liver 9.​ The cleavage results in the formation of complex and prevent recruitment of C9 -​ 3 riles of complement: C3bBb, which is the C3 convertase -​ Patients having terminal complement deficiency suffer -​ Killing (lysis) of foreign cells -​ C3b bound to microbial surface converted C3 convertase from pathogen infections >> recurrent infections -​ Tagging foreign material (opsonising) that will become an amplification loop -​ Proinflammatory signalling and chemoattraction Terminal Complement pathway 3 Pathways of complement 1.​ Formation of C5 Convertase -​ All pathways will meet and make C3 convertase and ​ From the Alternative Pathway: formation MAC (membrane attack complex) ○​ The C3 convertase (C3bBb), generated in the -​ Types of pathways alternative pathway, binds an additional C3b -​ Classical pathway molecule to form the C5 convertase -​ Starts with antibody (C3bBbC3b). 1.​ C1 Complex: C1q [large hexamer], 2 proteases - ○​ C3a induces local inflammatory response C1r and C1s ​ From the Lectin Pathway: 2.​ C1q, containing 6 globular heads, each bind Fc ○​ The C3 convertase (C4b2a) from the lectin (or region of antibody classical) pathway similarly binds an additional 3.​ After 2 antibodies bound >> activate C1r and C3b, forming the C5 convertase (C4b2aC3b) C1s ○​ C3b: high reactive thioester bond in C3b 4.​ C1r cleaves [cuts] C1s covalently attaches to microbial cell via 5.​ C1s binds with C4 >> cleave into C4 and C4b expose -OH/ NH2 groups; 6.​ C4b attaches [covalently] to bacteria >> binds ○​ free C3b rapidly inactivated by hydrolysis C2 2.​ Cleavage of C5 7.​ C1s cleaves [cuts] into C2a and C2b ​ The C5 convertase cleaves C5 into two fragments: 8.​ C4b and C2a make active protease C4bC2A = ○​ C5a: A powerful anaphylatoxin that recruits classical C3 convertase and activates immune cells. -​ May bind to bacteria surface directly [lipoteichoic ○​ C5b: The starting point for MAC assembly. acids and other proteins etc] ​ Nucleats the MAC -​ Lectin pathway ​ C6,7 and 8 recruited to the membrane -​ Start with a lectin ​ C8 inserts and C9 forming cylindrical pore -​ Mannose binding lectin (MBL) produced by liver (esp during inflammation) Bacterial death [results of a hole something under pressure] : -​ Binds repeating mannose (bacterian and yeast) -​ Forming bores in outer membrane >> let antimicrobial -​ Lectins [proteins] binds to carbohydrates enzymes enter -​ MBL-associated serine protease [MASP] -​ Affecting function of inner membrane 1.​ MBL binds to bacterial surfaces -​ >> cytosol leakage, bacterial lysis and cell wall instability 2.​ MASP1 cleaves MASP2 -​ Protein gradient >> high active against G- (eg Neisseria) 3.​ MASP2 cleaves plasma located C2 and C4 Completment - function 4.​ C4b attach to surface [covalently] -​ Tag microbe (opsination) 5.​ Combines with C2 aa giving C4bC2a = c3 -​ Opsonins - tag for immune system convertase -​ C4b and C3b covalently attached to bacteria -​ Alternated pathway -​ Acts as ligandfor Complement Receptor -​ Does not need antibody/microbe to start -​ Alert immune system (inflammatory response 1.​ C3 in blood is hydrolysed >> C3(H2O) -​ Lyse invader 2.​ C3(H2O) binds to Factor B Cleaved ‘a’ products [analphylatoxins]: 3.​ C3(H2O) bounded to Factor B cleaved by -​ Binds to specific receptors on immune cells Factor D >> Bb and Ba  -​ Cell-mediated response -​ Recognising antigens - carbs, lipids, DNA and proteins Lecture 05: antibodies and adaptive immunity ​ -​ When injury happens etc Antibodies part 2 -​ Macrophages, neutrophils and complement helps T-cell Receptor [TCR] -​ Recap aand continuation : -​ Dendritic cells in epithelial tissues -​ Similar to antibodies -​ All antibopdies produced in B cells -​ Antigen presenting vells -​ Has only 1 binding sire -​ All b-cells are made in the bone marrow -​ Found in external-facing tissue -​ recognises peptide antigen present by cell -​ Each B-cell clone produce a different antibody -​ Dendrites [long cytoplasmic projection] -​ Made using same gene arrangements like antibodies -​ IgD class = B-cell receptors -​ In pathogen recognition receptors [PRR] -​ Description of receptorL -​ Variable (v) region differe from different antibodies -​ When exposed microbes and cytokines, -​ 2L [L-shape] -​ Constant region remains constant activatess DC and migrates to lymph -​ Alpha chain and beta chain joined tgt by used -​ Adaptive immune system is not inherited by made nodes to present to antigen disulfide bridge de novo -​ Lymphatic system and lymph nodes ​ -​ Creating an antibody -​ Lymph fluid travels around the body thats driven B cell activation, clonal selection and the secretion of -​ B-cell made in bone marrow by muscle movement antibodies -​ In differentiation -> each B cell makes a different -​ Antigens presented to B-cels and T cells in lymph -​ When antigen are delivered into lymph nodes antibody by making own antibody gene nodes -​ 1. Antigen is recofnise by naive b-cells via BCR -​ Antibody found in segments on the chromosomes -​ DC and macrophages presented to antigen -​ 2. When antigen find specific B-cell, B-cell is then -​ Different segmentation -​ Pathway: activated and replicate quickly 0making b cell -​ 30-45 variable [V] gene segments -​ 1. External facing barriers breaches clones -​ Variable and constant gene segments -​ 2. Microbes enters -​ 3. B-cell clonses differential into plasma cell or -​ Several joining (J) gene segments -​ 3. DC engulfs and displays the antigens memory cells -​ Heavy chain has several Diversity (D) gene -​ 4. Antigens presented in lymph nodes [ -​ Production range of antobody classes recognising segments soluble antigens in the blood stream will original -​ Each B-cell clone will have it own variable region go to the spleen] -​ plasma cells for light aand heavy chain -​ 5. Naive B cells bind to antigen and -​ 5-6 days after infections -​ Generating diversity: become activated -​ Prod a lot antibodies -​ Combinatorial diversity: -​ 6. Native T cells bind to antigen and -​ Some mature plasma cells remain in bone marrow -​ Genetic recobintion between V+J+D [heavy] become activated​ producing low level antibodies and V=J [light] -​ Memory b cells -​ Junctional diversity: random mutations at B-cells and T-cell The lymphocytes -​ Same membrane bound antibody as activated junctions of the segments’ -​ B cells produces and secrete antibodies - therefore parent b0cell -​ Somatic hypermutations: continues mutation on humoral immunity -​ Providing life-long immunity an antibody -​ B-cell mature in bone marrow -​ Responds very quickly to same antigen = no -​ When B cell bind to an antigen: -​ T cells detecting and kill infected cells cell mediates symptoms -​ Massive proliferation of B-cell clone immunity -​ Rapid response to second infections -​ Antibodies have secreted (adaptive -​ T cells mature in thymus -​ Vaccine work immunity) -​ Both originate from stem cells in bone marrow -​ Tricking immune system to make -​ In the lymph nodes, b-cell close make -​ Both migrate to lymph nodes waiting to be activated antibodies against the vaccines new mutation in variable region ​ -​ Producing memory cells to prevent real increase antibody affiinity Receptros define each B-cell and T-cell infections​ B-cell receptors: The adaptive immune response -​ Description of receptor: -​ Immune system remembers due the adaptive immune -​ 42Y response -​ 2 heavy chains -​ Vaccine works due to memory -​ 2 light chains -​ Memory is controlled by B cells and T -cell -​ Pair of light and heavy chain makes on antigen [lymphocytes] binding site (x2) -​ -​ Chains are connected through disulide bridge -​ 2 types -​ Antigen binding site are at the variable region -​ Humoral response [antibodies] -​ BCR [b-cell receptor] are membrane bound antibodies [IgD]  ​ Lecture 06: T-cells and B-cell activation T-cells -​ Clonal expansion T cells -​ Mature in the thymus -​ Activated by DC proliferation 1-2 days -​ TCR [t-cell receptor on its surface -​ Effector cells [Th CD4 / Tc CD8] are activate leave -​ Each t-cell recognise different antigen and recognises lymphoid tissue antigens presented on surface on infected cells -​ Importance of Th cells -​ Effective against viruses and intracelullar pathogens -​ Allow B-cells to convert into plasma and memory cells -​ Types -​ Stimulate Tc cells to proliferate and kill other infected -​ Cytotoxic T cells [CD8 / Tc cells] cells [ eg - IFN gamma and TNF-a ] -​ Kills cancerous/infected cells -​ Activate macrophages to kills -​ Helper T cells [CD4 / Th cells] -​ HIV targets CD4 cells = no effective immune system -​ Activates immune system with cytokes ​ -​ T cells recognises infected cell B-cell and T-cell activation -​ Antigens presented on infected cells -​ Afer making, naive T cells and B cells migrates to lymph -​ It can only recognise antigens presented on MHC nodes/spleen molecule [major histocompatibility complex] -​ Continue to circulate in the body -​ Antigen presentation by our cells -​ Upon infection -​ MHC1: all nucleated cell our body has -​ 1. Microbes enter -​ To display cells -​ 2. Antigens could be presented in lymph nodes -​ Foreign proteins digested by proteasome (DC) -​ Foreign peptides delivered via ER to MHCI -​ 3. Free antigen could enter blood > spleen -​ Recognising by Cytotoxic T cells that kills the cell -​ 4. T cell and B-cells will recognise antigen and -​ 1. Infected cell presents antigen on MHC 1 become activated [presentation] -​ Antigen entering lymph nodes -​ 2. T-cell recognises it in infected tissue via -​ B-cells look for free antigen in lymph nodes T-cell receptor [recognition] -​ Enters and sorted based on molecular size -​ 3. Tc cell kills infected cells [granenzyke -​ Lymph node macrophages: viruses and and perforin] very large antigens -​ MHCII: dendritic and macrophage has -​ Lymph fluid: soluble antigens [small] -​ Surveillance and trigger -​ T-cells looking for DC cells presenting antigen -​ Microbes digested in phagosome -​ Look through all DC cells in 24 hours -​ Microbial peptides loaded on to MHC II and -​ If no antigen detected -> moves to next nodes present at cell surface -​ If detected: T-cell clones is activated -​ Recognized by Th cells -> secretes cytokines to -​ If soluble antigen detected: B-cell close will wait to activate APC [ antigen presenting cell ] be activated by Th cell -​ 1. DC present antigen on MHCII in lymph -​ B cell activation nodes [presentation] -​ 1. If antigens detected - B cells stays in lymph -​ 2. Th are activated node -​ 3. Releasing large amount of cytokines to -​ 2. T-cells proliferate into Tc cells and Th cells - activate immune cells clonal selection -​ Antigen presentation [summary/overview] -​ 3. B cells - IgD binds with antigen then engulds it -​ 1. Infection -​ 4. B cells process antigen and present via MHCII -​ 2. DC present antigens to T-cell in lymph nodes -​ 5. Within 48h, B-cell found Th cell with correct -​ 3. T-cells activated and released TCR -​ 4. Tc cells kill any infected cell -​ 6. B-cell now activate and makes plasma cell -​ 5. Th cell activates DC/macrophages presenting the -​ B cell activation and proliferation takes 4-7 days in lymph antigen nodes to make plasma -​ 6. Memory t cells produced​ -​ Produces 5000 plasma cells ​ -​ Makes 5 classes of antibodies (GAMED) Lecture 07:The Mucosal Immune Response -​ detecing/destroing pathogen organism that gains -​ Peyers patches: Intestinal mucosa [dome-like structures] Basics: entry via gut -​ Has lymphoid tissues = key sites for coordinating -​ Mucosal immune system (MIS) -​ Have beneficial effects of commensal microbes immune responses [ B + T cells, dendritic cells ] -​ for protecting toxic elements that enters via mucous Regulation of gut immune homeostasis -​ Removing pathogens and maintain tolerance, membranes -​ Dendritic cells [DC} critical for maintain immune commensal bacteria -​ Largest immune organ homeostasis in the gut -​ Villi has network of blood vessels -​ Single later epithelium -​ 1. DC - sampling antigen, process and present to -​ Transporting nutrient from food to rest of body -​ Covered by mucous and anti-microbial proteins T cells -> leading to activation of anti-inflammation -​ Lamina propria: inside villi, lose connective -​ Reinforced by innate and adaptive immunity response, aidinfg in maintenance of immune tissue -​ Microbiota: commensal, symbiotic and pathogenic homeostasis -​ Crypts which contain stem cells -​ Found in gut, skin and nasal and oral cavities -​ 2. DC travels to peyes patches, presenting antigen -​ Epithelium and mucous: form protecting layer against Inductive and effector sites to T cells and stimulate their differentiation to microbes -​ Divided between the 2 based anatomical and functional Tregs [ T regulation cells ] -> disrupting of Tregs ​ properties function is associated as immune tolerance is Pathogenic infection -​ Inductive: changes -​ basics -​ MALT: mucosa-associated lymphoid tissues -​ 3. T cell move to lamina propria of the villi through -​ Dysregulation / breakdown of homeostasis in gut may -​ Providing cont source of activated memory B cells lymphatic system - secreting IL-10 lead to inflammation and T cells >> moving to effector sites -​ DC responsible for starting all antigen specific response -​ Caused: mechanical, chemical and pathogen factors -​ GALT: gut-associated lymhoid tissue -​ Antigen presentation regulated tolerance via: -​ Bacteria activates epithelium = bacterial influx -​ NALT: nasopharyngeal-associated lymphoid tissue -​ Deletion of auto reactive T-cells -​ Releasing IL-25 - activating immune cells -​ Effector: -​ Induction of anery [lack of response] -​ IL is always available/secreted due to cellular -​ Sites inclusive of gastrointestinal, upper respiratory, -​ Treg expansion damage. reproductive tracts and respiratory tracts -​ Regulators of immune system - linking microbial -​ Innate lymphoid cells in gut pathogen defense -​ Contains antigen-specific mucosal effect cells sensing feature of innate system to specific -​ Innate immune lymphoid cells [ILCs] is necessary for -​ Eg: antibody producing cells, naive memory B and T adaptive response immune response and maintaining homeostasis cells -​ Tregs - (WBC): controls, suppress, inhibit activity of -​ Three subsets: -​ Lamina propria regions of GI other T cells -​ 1. ILC1 - response to tissue inflammation, virus, -​ Areas -​ Types: bacteria and certain parasites -​ Microbiota in the MIS - commenasl, symbiotic and -​ Induced Treg [iTregs]: targeting foreign -​ Has NK Cells pathogenic microorganisms antigens and neoantigens -​ IL-12: drives activity and causes group to Mucosal immunity -​ Natural treg [nTregs]: works to control produce IFN-y -​ For protection against toxic elements that enter via autoimmune inflammation -​ Innate counterpart of T helper cells 1 cells - mucous membrane -​ Characterized by CD25 - increase TGF-B and non-cytotoxic [ potentia; NK-like cytolytic -​ Largest organ IL-10 activities] -​ Single layer epithelium covered by musuc and -​ Immune system would react in excess causing to -​ ILC2 - contributing to response of helmint [ anti-microbial proteins (reinforced by innate and attach its own cells when Tregs is absent parasitic worms] adaptive) -​ Early stages of IBD - imbalance immune response and -​ Response to IL-25, ILC2s produce protein to Mucosa immunity in the gut gut inflammation = broken mucosal barrier induce mucus production from goblet cells -​ Gut mucosa has largest immunological environment of -​ Causes: -​ Activates DC that prime effector T cells and body -​ 1.Increase intestinal permeability recruit mast cells and eosinophils -​ Immune cell maintain homeostasis and projects agains -​ 2. Antigen translocation to lamna propria -​ Causes muscle contraction and expulsion of prolonged inflammation -​ 3. Entry to circulatory system works -​ Key roles: -​ 4. Increased number of resident immune -​ ILC3 - interacts with DCs to maintain gut -​ Providing protection against pathogenic bacteria in cells [DC, macrophages, Th1, Th2, Th17 and epithelial barrier the gut B cells -​ Encounter antigen from gut microbiota causing -​ Nutritional role - synthesizing key vitamins -​ 5. Progression of inflammation DC to secrete IL-34 producing IL-22 -​ Microbes can be detrimental Organisation of gut IS -​ Il-22 activates epithelim - secreting -​ Evolved mechanism -​ Villi - intestinal surface covering with finger-like anti-microbial peptides killing bacteria -​ Avoiding negative response from food antigen projections -​ Interacts macrophages to induce gut immune -​ Helps with nutrient absorption homeostasis -​ Largest population of immune cells  -​ ​ ​ ​ -​ Pathways ​ -​ 1. Surrounding tregs stops anti-inflamatory cytokines ​ production and facilitate inflammation Molecular Targets -​ 2. DCs becomes activated and secrete key -​ Healing inflamed mucosa and restoration of barrier inflammatory cytokines IL-6,12 and 23 function = goals of therapy -​ 3. Effector T cells escalate immune response -​ Structural chance in IECs due proinflammatory increasing secretion of pro inflammatory cytokines cytokines (TNF, IFN-y and IL-3, all increased] [TNFa, IFNY and IL17] -​ Response is low -​ 4. Neutrophils recruited - Clearance, achieved by cell death NETosis -​ Neutrophils producing extracellular traps [NETS[ -​ NETs kill bacteria damage to tissue - Epthelial integrity restored - damaged cells are replaced with cells from stem cell on intestinal crypts Mucosal immunity and treating disease -​ Dysregulation =disease -​ conditions : autoimmune disease, IBD, allergies and infections -​ MIS used to developed effective therapices Vaccination -​ Pathogen enter the body through aerodigestive and reproductive tract -​ Mucosal vaccines - treating cholera, salmonella and poliovirus -​ Function: -​ M cell in follicle-associated epithelium [FAE) take vaccine antigens -​ Vaccine antigen then transferred to antigen presenting cells [APCs} -​ Processed and presented to CD4 and CD8 T cells -​ Mucosal vaccines induce rapid immune response [betweenn 48-72h] -​ Negatics: contains microorganism which toxin-like molecules =adverse immune response Treating immune cells -​ Key diseases = structural damage to bowel wall -​ IBD mediated dysregulation of MIS -​ Crohns disease [CD} -​ Ulcerative colitis [UC] -​ Key gut cells signal receivers: Intestinal epithelial cells [IECs] -​ Regulated by: Cytokines, TLR ligans and growth factors -​ Signal affect: apoptosis and proliferation -​ IBD = inflamed mucosa and alterations in barrier due to IEC Lecture 08:Allergens -​ -​ Anaphylaxis [severe, life threatening allergic -​ Allergen sources: pollen, fungi, insects, domestic animals -​ Grass pollen reaction] and food sources -​ Properties of windborned pollen reflects -​ Occurs within seconds or minutes of exp -​ Allergen source eg grass poller grains = hay fever their role -​ Resulting - immune release -​ High IgE test result = indication of allergy -​ Released: windy,dry condition - carried -​ Histamine -​ IgE = indication of allergic reaction by wind -​ Neutral proteases [trypase and Aerodynamic properties of allergens -​ When contact with wet surface >> chymase] -​ Grass pollen allergens release proteins = pollen tube - human -​ Proteoglycans (eg. heparin) -​ Inhaled -10ng/day IgE response -​ Symptoms: -​ Eluted from grains -​ Main grass related allergen - LOL p1 -​ Causes body to go in shocks: -​ Becomes airborne after dsturbance -​ Pollen allergens - IgA and IgG antibody 1.​ Blood pressure drops -​ Major inhaled allergens have source that becomes response 2.​ Airway narrows = block airborne and molecules that are present -​ IgA: mucosal immunity and breathing -​ Protein epitopes are main target for IgE antibodies neutralization (found in saliva, tears -​ Rapid weak pulse Allergen from domestic animals and mucous) -​ Skin rash -​ Cat felis and domesticus -​ IgG: opsinatiozation, neutralization, -​ Nausea and vomiting -​ Cat allergen antigen - Fel D1 complement activation and -​ Treatment: -​ Protein is airborne all the time antibody-dependent cellular -​ Injection of epinephrine and follow -​ Inhales 1ug of Fel d1/dat - eg 100x quantity of cytotoxcity [engage NK cells to kill up to A&E mite/pollen allergen antibody coated target cells] Allergen exposure -​ Testing: 90% individuals who are allergic to cats had IgE -​ Dust mites -​ Transdermal route antibody response to Fel d 1. -​ Main allergen Der P1 - found in fecal -​ proteins applied to skin can induce inflammation -​ Skin testing/serum testing for IgE particlas -​ Allergen to skin cause local infiltration of -​ Skin prick test: small amount of cat allergen place on -​ Mite feal pellets eosinophils and basophils skin >> skin broken fro entry -​ Wide range of substances -​ Eczema - high skin permeability - high levels of IgE -​ Symptoms: nasal, eye and lung symptoms within half -​ Act on pathways triggering innate antibodies an hour of less of entering a house with a cat s response (incl - TLR4 and TLR9) -​ Stinging insects - honey bees, jumping ants and fire -​ Assay for airborne gave an explanation for physical -​ Toll lik receptor activation = pro ants reaction, particles are smallers than mite inflammatory cyctokens and -​ Different insects different response particles/pollen grains inflammation -​ Bee venom - respond systemically -​ Floats for long period of time with little/no -​ Cat dander -​ Fire ants stings intense local response in skin disturbance of air or anything sticky -​ Main allergen - Fel D1 targeting IgE >> sensitization and IgE antibody production -​ Easily transferred on human loathing to public places when inhaled -​ Sublingual route Sensitisation -​ Steps in active immunization of cats -​ Oral route - exposure induce tolerance, eating wide -​ Immunisation does not induce persisten igE response against Fel 1 range of doos, 95% of population no allergic reaction -​ 2 routes of IgE production (antigen intro) 1.​ Vaccination Fel-CuMV -​ Food with different proteins (eg - ovalbumin -​ Early animal research - low dose, most vaccines capable of inducing sensitisation and IgE effective 2.​ Activation of immune antibody production) -​ Later research - CFA-antigens + emulsion system -​ Immune deviation agent = more IgG antibody response - IgE 3.​ Activate B cells secrets -​ Experiment: test if oral exposure of antibodies = germinal centre - microstrcutre anti-Fel D 1 antbodoesi chemical cound induce sensitivity long antibody 4.​ Anti-Fel D1 IgG circulate -​ Result: oral exposure of mice to chemical -​ Allergic specific reactions: through cats body and would induce prolonged tolerance to -​ Types of allergy symptoms binder the allergen Fel D1 exposure by transdermal route ​ -​ Trouble breathing >> lowering ​ -​ Itching reactontogenicity in cat ​ -​ Sneezing secretions ​ ​ -​ Headache ​ ​ -​ red/watery eyes ​ ​ -​ Hives or rash ​ ​ Immune Mechanism that underlie allergie sensitisation -​ Th9 and 17 - microbial -​ Allergic sensitisation - manifestation of immune -​ Th2 - anaphylactic food allergy - peanut processes that is mediated by pathogen Th2 effector -​ IL-5: indented, eosinophilic gI dieases cells -​ Nature of T-cells resp are highly heterogenous -​ Th2 - secrete cytokines [IL-4,5 and 13] Takeawats from injected allergen -​ Effects recruitment of inflammatory cells to -​ IT - increasing dosing regime of allergen extract proved sites of allergen exposure clinically >> immune response move away from th12 -​ Resulting - in hypersensitivity and mucous secretion response [protective response] -​ IL-4 induces IgE class switching - key -​ Tregs to hold key dev in tolerance switching to mast cell activation and -​ IL10 increase (anti-infallmatory0 inflammation -​ Reduce T-cell proliferation Allergens as ligands for pattern recognition receptors -​ Reduct Th2 cytokines -​ Dendritic cells (DCs) - initiate o Th2 response to allergen -​ Mehcniasm increase IL4 + IgGA - suppresses igE -​ Has various surface receptors influencing -​ Increase IgG - blockers binding of allergen to B-cells and function and T-cell outcomes modulating delivery to APC >> lowering T cell resp -​ Microbes inhibit allergen-induced Th2 response Site of exposure and allergen dose -​ Shown in mice -​ Site and dose: driver of T-cell mediated inflammatory -​ Allergen + lipopolysaccharide (LPS), treated disorder with different doses of bacterial products that -​ Dose: depender on allergen delivery efficiency to APCs - affects T cell outcomes relating to exposure of mechanism -​ LPS -​ Site - central role of DCs, [possibility of easy migration? -​ High dose: LPS resulted in Th1 response -​ Common sites - skin, respiratory, mouth and -​ Low dose: LPS favoured Th2 gut -​ Found carbs receptors facilitate binding to 1.​ Intersite sensitization example allergens to DCs a.​ High prevalence of eczema in asthma patiene Protein sequence and T-cell response to allergens i.​ Th17 implicated via activation from skin - -​ Allergen with immunodominant T-cell epitopes: causes lung disease following sensitisation recognised by atopic and non atopic subjects with through skin HLA-diverse haplotypes ii.​ [skin] microenvironment for activeting DCs, -​ Epitope: portion of antigen capable of increase T-cell resp to allergens stimulating immune response b.​ Genomics -​ T-cell epitope - protective: induces regulatory i.​ Gene coding filaggrin mutates compromising cytokine IL-10 skn integrity -​ Cat allergen (Fel D1) - specific population of T ii.​ Common causes - DC activation via multiple cells (chain 2) > allergic individuals surface receptors = different effector T cells at -​ How protein sequence effects allergic response: features lesion in skin (Th2 and Th17) different allergen is important to Th2 initiation and 2.​ Pro-telorgenos response in established disease a.​ Identifiable in oral cavity, populated by T cells -​ In vivo: intradermal injection of allergen b.​ Expression TGF- TGF-b, IL-10- IFN-c, Il-17 and DC peptides in cat-allergic asthmatics expressing , TLR2 and TLR4 -​ Result: worsen asthma c.​ Research - those receiving SLIT [sublingual -​ Meaning: role th2 cells defined, TCR immunotherapy] showing exposure to allergen in specification in disease pathogensis pral cavity favors tolerance induction that is -​ implication - injectioning of single peptide can mediated by resident APCS can activate memory Th2​ Other influences on the quality of the T-cell response to allergens -​ allergens :multiple factors contrinbuting to Th2 responses: type, dose and pathways -​ Th2 responses plays in dev of allergic disease - T cell response differs depedning on type and staf Lecture 09: Immune System Disorders -​ White blood cell - buffy coat​ -​ Face: low set ears, small jaw bones that The Immune System 0 reced, wide-set eyes and cleft palate​ Key terms -​ Various Test -​ Pathogens: microorganism causing illness -​ Full blood count [FBC] -​ Thymus gland -​ Commensals: live with host causing no damage -​ Packed cell vol [PCV[ -​ Needed to normal dev of T cells -​ Infections - habouring and multiplying of pathogens in -​ Total protein [PT[ -​ Gland missing/underdeveloped, nu. Of host -​ HbA1c T cell is low = limiting ability to fight -​ Primary infection: developing in host -​ CRP - cardiac marker many infection -​ Cytology - blood smear, cell morphology, -​ Infection begin after birth and can recur -​ Reinfection: same organism same host monitoring parasies and bacteria -​ Bruton agammaglobulinaemia: immunodeficiency state -​ Secondary infection: same host different organism White blood cell disorders associated with lack B-cells [no antibody production] -​ Disease causing organisms: -​ WBC count too low/high/not functioning properly -​ Infomations: -​ Pathogen [disease causing]: Bacteria, virus, -​ Absence of the thymus [Di George syndrome] - -​ Genetic immune system disorder bacteria and parasites associated with lack of T cells [no cell-mediated -​ Reduced ability to infections -​ Pathogens causing illness: immunity] -​ No symptoms first few momths -​ Toxins - harmful substance produced by -​ Basic info: -​ Infection of the pathogen -​ Immunodefienct disorder: chromosal -​ Inner eat -​ Reproduction: multiplying pathogens that abnormallity, doesnt run in the family -​ Sinuses damage cells - using resource cell needs to -​ Born with several abnormalities: -​ Respiratory tract survive -​ Heart defects -​ Affecting males - mutation in bruton’s -​ Immune response - causing inflammatory -​ undeveloped/absent parathyroid tyrosine kinase response [swollen, sore, increase blood flow glands and thymus gland -​ BTk in b develipemt through B cell -​ Pathogen transmission types -​ Facial changes - low sitting ears, receptor signalling -​ Food and water cleft pallets, fish shaped mouth -​ Recurrent infection may cause organ -​ Direct contact -​ diagnosis damage, -​ Insect bites -​ 1. Blood test -​ Chronic lung disease -​ Airborne droplet -​ 2, imaging test [chest x-rays and -​ Increase risk of certain cancers -​ Indirect contact echocardiography] -​ Infection arthritis -​ Vertical transmission [not in slides] -​ Symptoms [suspected based of; -​ Symptoms: -​ Zoonotic transmission [not in slides] -​ Total nu. T and B cells -​ First months: protected by antibodies given -​ Nosomial transmission [not in slides] -​ T- cells and parathyroid gland are by mother -​ Sexual transmission [not in slides] functioning -​ Later in lifes: babies developed severe, -​ Feacal-oral transmission [not in slides] -​ Production of anutbdues recurrent bacterial infection s Immune system consisting off -​ Chest x-ray taken to check size of -​ Infection in ear, lungs and sinus -​ Initial defense [physical barriers] - skin covering and thymus gland -​ Male infants with XLA have mucous membrane where line digestive and respiratory -​ Affects heart = echocardiogram used -​ Very small tonsils tracts, nose hairs -​ Treatment -​ small/no lymph nodes -​ 2nd line [innate immune system] - no adaption to -​ 1. Calcium and vitamin D supplements - -​ Infectious mononucleosis pathogen; involving macrophages, neutrophils and NK orally given to prevent muscle spasm -​ Viral - body able to produce excessive number of cells -​ 2. Transplantation of thymus tissue or stem WBC, [EBV able to weaken immune system -​ 3rd line [adaptive immune system] cells - possible cure -​ Has swollen lymph nodes, fever, sore throat and -​ Adapts to specific pathogen [varying receptors] -​ Surgery maybe needed to prevent heart extreme fatigue -​ B cells make antibodies - new antigens failure/death -​ Able to spread via saliva -​ T cells mediate cellular response using varios -​ Abnormallities: -​ Symptoms take 4-6 to appears, does not last receptos -​ Heart: children born with congenital heart more than 4 months Blood disorder -​ Treatments: rest and liquids -​ Blood centrifuged is separated by density -​ Parathyroid gland: children born with -​ Once infected, virus remains dormant in throat -​ Hematocrit [packed cell vol] is total percentage blood underdeveloped or no parathyroid gland and blood cells forever volume occupied by red blood cell [regulating calcium levels -​ Steps -​ Men [42%] women [45%] -​ Low calcium = muscle spasm -​ 1. Epstein Barr Virus [EBV] first infects epithelial cell in pharnyx  -​ 2. Causing pharyngitis, followed by -​ Babies shows no symptoms as protected by -​ (2). Following the release of viral genome infection in B cells antibodies passedm mother and enzymes create RNA-DNA hybrids -​ 3. Once in B cell, it replication and B cell -​ FIrst signs: -​ (3). The viral dsDNA is translocated into proliferate. T cell response to the B cellis -​ Regular infections [coughs and colds] the nucleus and integrated into the host initiated -​ Thrush [infection by yeast candida] in genome -​ 5. Increase in lymphocytes mouth and or nappy area -​ (4). Transcription factors transcribe the [lymphocytes] -​ Poorly fed proviral DNA into genomic RNA - moved to What can go wrong with your immune system? -​ Germs in env may cayse serious illness in cytoplasm (5). In the cytoplasm, host-cell -​ Working not as it should = immune disorder child ribosomes catalyse synthesis of viral -​ types -​ Virus cytomegalovirus [CMV] - causes precursor proteins -​ 1. Primary immune deficiency = born with weak severe infections [pneumonia is -​ (6). HIV RNA and proteins assemble immune system frequent] beneath the host-cell plasma membrane - -​ 2. Acquire immune deficiency = getting a disease -​ Parasite cryptosporidium [sometimes form viron buds (7). Maturation occurs in that weakens your immune system found in drinking water] causing severe the forming buds - can infect another host -​ 3. Allergic reaction = immune system being too diarrhoea cell active -​ Chicken pox [varicella] and cold sores -​ Innate immune response to HIV -​ 4.autoimmune disease = immune system fighting [herpes simplex], dangerous for babies -​ Encountering Inate immune cells firs: against you with SCId -​ Macrophages -​ Severe combined immunodeficiency [SCID] -​ Diagnosis: presented to GP - usually poor -​ Targets cells for HIV -​ information weight gain or feeding problems -​ Habour virus: sources of viral proteins -​ Rare and inherited disorders causing major -​ Treatments -​ Losing ability to ingest/kill microbes abnormalities in IS -​ 1. Hematopoeitic [blood forming] stem cell -​ Presenting antigen to T cells - major -​ Greatly increased risk of infection and other plantations - standard treatment cause of immune response life-threatening complication -​ Partially restored immunity - received -​ DC [dendritic cell] - presenting antigen to T -​ Treatment available may cure from a sibling who is close tissue match lymphocytes in lymph nodes -​ Types: genetic causes, lymphocytes missing -​ Research show that early transplantation -​ Early cell combating HIV at mucosal or not function is critical, before 3.5 y.o. To mostly likely -​ Transport HIC to lymphoid tissue -​ 3 main types lymphocytes affected: T-cells, survive -​ Key antigen-preenting cell trapping B-cells and NK cell -​ 2. Children who have SCID with ADA have present antigens on cell surface -​ Causes treated with partial success with PEG-ADA -​ NK cells [natural killer] - lyitc activity against -​ Inherited, caused by mutation in child’s [enzyme replacement therapy cell have low MHC genetics -​ 3. Possibility use of gene therapy for some -​ Aids when HIV escapes cellular -​ Common in infants - mutation causes ttypes immune response absence of a protein that needed to -​ Stems cells obtained from patients bone -​ Proliferates in response to type 1 development of WBC marrow interferons secreted by DCs -​ Different genes can be affects [hence -​ Normal cells inserted into stem cells -​ Releasing cytokines, interfrons y different types] using vector [IFN-y] and TNF-a -​ Genetic test enables to test for specific types - -​ Corrected cell returned to patient to -​ Inhibiting viral replication by releasing types based on protein/gene affected restroe tcell function IFN-y -​ Common gamma chain frequency HIV [human immunodeficicy virus] , retrovirus and causative agent -​ Cellular immune response to HIV -​ Adenosine deaminase [ADA] deficient of AIDS [acquired immunodeficient syndrome] -​ Cell mediated -​ JAK 3 kinase deficiency -​ HIV invades immune cells [T cells and monocytes] = -​ Activated on entry of HIV into T cells and -​ MHC class II deficiency reductionin numbers and loss cell-mediated immunity viral proteins synthesis -​ Immporta to exact type as management and -​ HIV invasion of immune cells - -​ MHC 1 on cell surface display degraded HIV treatments as: -​ infection of T cell assisted by T-cell peptide fragments for recognition by T-cell -​ Some conditions treatments are co-receptor [CXCR4] receptors (TCR) on CD8+ T cells avaialble -​ HIV infects monocytes by intersecting with -​ CD8+ cells lyse infected HIV cells and -​ Allowing accurate genetic counselling CCr5 co-receptor secrete cytoknes [IFN-y, TNF-a], inhibiting for future pregnancies -​ Steps: show in diagram: virus and blocking viral entry -​ Symptoms and diagnosis -​ (1). Nucleocapsids containing viral genome -​ In early stages of infections, CD4+ cells lose and enzymes enters the target cell proliferation capacity hence have little  contribution to viral contribution ​ -​ Humoral -​ Occurs later in infection -​ Neutralising antibodies specific to protein involving virus entry and controlling infections -​ Antibodies specific to: -​ Variable region of GP120 (V3) -​ CD4 binding site and chemokines receptor [eg - CXCR4 and CCR5] -​ Transmembrane protein GP41 -​ Why does Immune system fail to fight HIV? -​ Reasons contributing tofailure of immune system controllin gHIV infection and preventing aids -​ Infecting CD4+ cells, HIV can replicae in activate T cells - paralying one component of adaptive system -​ HIV able to establish latent infection in CD4 T cell and remain invisible = replication can occur later -​ Antigenic mutation w/i T cell epitopes can affect binding capacity of MHC molecules to vital peptides = inability TCRs to recognise MHC molecules -​ HIV can hide from anti-HIV antibodies by expressing non-immunogenic glycans on key antibody epitopes Lecture 10: Autoimmunity - Transplantation ​ function.​ Sex Difference General info: -​ Male - XY tissues -​ Classes: -​ Graft or transplantation: -​ Graft rejection - male tissue grafted to female -​ Class I: Includes HLA-A, HLA-B, and -​ Definition: transfer of living cells, tissues or organs as females does not have Y gene BUT HLA-C. from on part of the body to another or from one -​ Eichwald Silmser effect: Grafts from female to -​ Class II