Exam 3 PDF - Immunology Past Paper

CHAPTER 10 Understand what is meant by systemic immune system -what we have looked at previously, pathogens invading the skin Understand what is meant by mucosal immune system -pathogens penetrating mucosal surfaces (viruses) Be able to describe the difference between systemic and mucosal immunity...

CHAPTER 10 Understand what is meant by systemic immune system -what we have looked at previously, pathogens invading the skin Understand what is meant by mucosal immune system -pathogens penetrating mucosal surfaces (viruses) Be able to describe the difference between systemic and mucosal immunity ***IDRK -systemic: REACTIVE, inflammation is common -mucosal: PROACTIVE, inflammation is BAD Know what mucin is, what cell generated it, and its role mucin: glycoproteins generated by the mucosal epithelium to protect the mucosal epithelium LARGE collection/chain of polypeptides -can be secreted or membrane bound. when they are membrane bound they can easily trap microorganisms, then the mucins are kinda gotten rid of, which gets rid of the pathogen with it Know what a defensin is in this situation they are AMPs (anti-microbial peptides), they break holes in the lipid bilayers of pathogens Understand what is meant by ”commensal” organism -translated to "eating at the same table", benefits from the host but does not have a super close relationship with or cause harm to it -a commensal organism lives in harmony with us -it is like one step below a symbiotic relationship they help: -synthesize metabolites (vitamins) -break down fibers in food -inactivate toxic substances in food -provide a barrier on the gut that stops pathogens from benefitting from it's resources, acts like skin -triggers development of secondary lymphoid tissue Understand why even a commensal organism can become pathogenic -if they don't stay put? Know the roles of the following subsets of gut epithelia cells: enterocytes, goblet cells, paneth cells, intestinal stem cell AMPS (anti-microbial peptides): defensins, kill pathogens by disrupting their membranes. -these little ladies sneak into the pathogen's lipid bilayer and form a pore. bad for pathogen ILC (innate lymphoid cells): "may or may not care about" enterocytes: absorb nutrients goblet cells: make and secrete mucus paneth cells: secrete AMPS (like defensins) ISC (intestinal stem cell): Lamina propria: connective tissue under the epithelium, where effector cells reside, aka effector compartment villi: increased surface area, great for nutrient absorption isolated lymphoid follicles: consist of mostly b-cells inductive compartment: tissue directly beneath the epithelium, where adaptive immunity is induces Know what the term gnotobiotic means germ free :) -not good Know what an M cell is and understand its function M-cells: transport microbes/antigens into the intestine Know what an intraepithelial lymphocyte is and its role IEL (intraepithelial lymphocytes): essentially cytotoxic t-cells in the epithelium Understand the role of Peyer’s patches a secondary lymphoid organ integrated into the wall of the small intestine. varies in size and number of germinal centers, T-cells, and dendritic cells Understand how intestinal macrophages differ in function from professional antigen presenting macrophages -they dont secrete cytokines, no inflammatory response Understand the term “oral tolerance” and how it is achieved (in general terms) -no immune response from food, even though it is foreign it is allowed Tregs, supress immune response to food antigens What are the distinctions between the two subclasses of IgA -mucosal vs systemic IgA -more somatic hypermutation in mucosal -differences in their hinge regions, longer = more susceptible to cleavage Above all remember that the MALT is all about NOT generating an inflammatory response and know the other basic distinctive features of the mucosal immune system CHAPTER 14 Terms to know: Hypersensitivity reaction: Allergens and Allergy: allergens induce a hypersensitivity reaction (allergy) Atopy and atopic: atopy is a genetic predisposition to allergy, when you have atopy (a genetic predisposition) you are atopic Anaphylaxis: caused by allergens in the blood, can cause organ damage and asphyxiation (death) Understand the process of a type 1 hypersensitivity reaction (what happens during first exposure and what happens during second exposure) -allergen binds to its specific associated IgE (previously bound a Fc receptor on a mast cells) resulting in degranulation (immediate hypersensitivity) -allergies we all have Know the properties of IgE the high affinity receptor for IgE (FceRI) properties: does not circulate in blood/lymph, taken up and concentrated in tissues, irreversibly binds to Fc receptor on mast cells Fc receptor: tetramer, one alpha chain that binds the IgE, and 3 signalling chains (one beta two gamma) that activate the mast cell Know the basic characteristics of Mast Cells and Eosinophils and Basophils -they all have high affinity Fc receptors -mast cells are full of cytotoxic granules (containing histamine), they secrete cytokines, covered in antibodies (against parasites or allergens), first encounter with allergen arms the mast cell, there is no reaction eosinophils: releases cytotoxic granules, kills parasites, damages tissues in allergic reaction. they are drawn to the site (where allergen is) when mast cells activate TH2 cells basophils: low levels in circulation, similar to eosinophils, release histamine and interleukins which cause damage in an allergic reaction. have a regulatory role in initiating a TH2 response Understand the basics of the PEFR test -used to diagnose asthma & determine if a substance is causing the asthma PEFR (Peak Expiratory Flow Rate) is measured Understand the strategy behind Omalizumab -decrease sensitivity -prevents IgE from binding to the Fc receptor, can only bind & block IgE before it has bound the Fc relector Understand the strategy behind AR101 (Palforzia) - desensitization CHAPTER 16 What are the six basic mechanisms that establish immunological self tolerance -negative selection of B cells in the bone marrow -negative selection of T cells in the thymus -thymus expresses tissue-specific proteins -lymphatic exclusion from brain, eye, and testis -induction of anergy in autoreactive B and T cells -Treg cell suppression of autoimmune responses autoimmune diseases are RARELY resolved or cured, only managed Remember the role of AIRE and understand why a defect or absence of AIRE would lead to autoimmune disease -AIRE presents non-thymus antigens to developing T-cells for negative selection to occur -lack of AIRE results in T-cells responding to tissue specific antigens Understand the relationship between FOXP3, Tregs and autoimmunity (in a very general sense) FOXP3: transcriptional repressor protein in T-regs a mutation in FOXP3 will affect Treg function, they can no longer calm the other T-cells down, so T-cells might react to self because the safety mechanism of the Tregs are broken Know that HLA is the dominant genetic factor affecting susceptibility to autoimmune disease and that women are more affected than men HLA genes account for 50% of genetic predisposition women are more affected, but not in a gnobiotic environment Understand that while every autoimmune disease can be related to type II, III or IV hypersensitivity reactions that there are many ways of categorizing autoimmune disease Understand how antibodies function as agonists or antagonists in autoimmune reactions agonist: pretend to be ligand, result in constitutive activation antagonist: blocks ligand binding Know in detail the mechanism of Graves’ disease and treatment AGONIST - constitutive secretion -overproduction of thyroid hormones (T3 and T4) -secrete TSH (thyroid stimulating hormone) treatment: removal of thyroid Know the mechanism of Myasthenia gravis and primary treatment ANTAGONIST -impaired signalling from nerve to muscle treatment: cholinesterase inhibitor -cholinesterase degrades acetylcholine (what the antibody antagonist binds to), so inhibiting this would result in more acetylcholine and thus more places for the signal proteins to have a chance to bind to without being blocked Know the basic principles of haemolytic anemia IgG and IgM bind to components of RBC, initiating the classical complement pathway, forming a MAC, lysis of RBCs Know the basic mechanism of Hashimoto’s thyroiditis and primary treatment -antibodies generated against the thyroid -hypothyroidism -opposite of graves disease treatment: thyroid hormone replacement therapy Know the basic mechanism of Goodpasteur’s syndrome and primary treatment -IgG antibody specific for collagen in kidney -inflammatory response is initiated -kidney function impaired/stopped treatment: removal of antibodies (dangerous), kidney transplant Know the basic mechanism of Multiple Sclerosis -myelin sheath of nerve cells is attacked -motor weakness, impaired vision, etc. Understand how the MAB rituximab works -binds to B-cells and targets them for removal Understand what is meant by molecular mimicry a chance resemblance to a structurally similar but not identical human epitope Know what is meant by immunological privileged site no lymph -eyes, brain, testis Understand what is meant by sympathetic ophthalmia if the eye is injured proteins unique to the eye will drain into lymph nodes where a T-cell response is activated, T-cells and antibodies will then come to the eyes via the blood stream. treatment: removal of damaged eye, immunosuppressive drugs CHAPTER 15 packed cells: antibodies have been removed Understand the terms: autograft, isograft (syngenic),, allograft (allogenic), xenograft All types of tissue transfer autograft: self-self isograft (syngeneic): twin donor allograft (allogenic): same species but not genetically identical xenograft: different species Understand the terms: histocompatible and histoincompatible histocompatible: HLA is similar between donor and recipient, thus a strong immune response is not generated histoincompatible: tissues between donor and recipient are significantly antigenically different, which results in an immune response and the donated organ/tissue is rejected parents can never receive a graft from their offspring, but offspring can always receive from the parents Understand the relationship between ABO blood group antigens and blood transfusion Type A: had A antigens. produces antibodies against B antigens Type B: has B antigens. produces antibodies against A antigens Type AB: has A and B antigens. produces no antibodies Type O: has no antigens. produces antibodies against A and B antigens everyone can receive type O blood, but people with type O blood can only receive type O blood UNIVERSAL DONOR people with type AB blood can receive ANY type of blood, but can only donate to people with AB blood. UNIVERSAL RECIPIENT Understand the relationship between RhD plus and negative compatibilities Rh+ Rh- blood transfusion -1st transfusion will induce production of antibodies against the opposing Rh type -2nd transfusion is when the problems occur, antibodies are made and immune response will occur sometimes an Rh- mother will have a fetus that is Rh+, this is okay for the first pregnancy, but if the mother gets pregnant again with an Rh+ baby the antibodies generated during the first one will attack the fetus and kill it. -can be helped using immunotherapy, preventing the antibodies from being formed Understand hyperacute rejection with respect to ABO antigens -if an organ is donated from a type A person to a type O person, type A antigens will be coating the organ. once it enters the recipient the A antibodies will attack the organ making it non-functional Understand what an alloreactive T-cell is and the terms alloantigen and alloreactivity it thinks the donated stuff is a pathogen Understand how an acute rejection of a kidney transplant occurs (including what is meant by direct pathway of allorecognition MHC differences cause the recipient's T-cells to become activated and attack the donor organ Understand the indirect pathway of allorecognition and chronic rejection takes a lot longer apoptosis of donor dendritic cells, MHC on the dendritic cells is degraded and presented to T-cells which activates them against the donor MHC Understand slide 26 in great detail; be able to explain what is happening in every frame of slide CHAPTER 17 Define: oncogenesis, metastasis, proto-oncogene, oncogene, tumour suppressor gene oncogenesis: process by which normal tissue becomes a tumor metastasis: when the tumor is able to invade neighbouring (or distant) tissues proto-oncogene: can/will receive a gain of function mutation (increased proliferation, mutation in the Ras pathway, resulting in constitutive downstream signalling) oncogene: a proto-oncogene that has undergone a mutation tumour suppressor gene: involved in regulating and constraining cell growth. mutations to the TSG can lead to cancer through unregulated cell growth. both copies of the TSG need to be inactivated through mutation for regulation to be lost. Understand the differences between malignant and benign tumours benign tumor: single localized mass malignant tumor: able to invade nearby tissue and undergo metastasis Know the multi-hit model -one mutation does not lead to cancer, it is multiple mutations within that original mutation that allows the tumor to outcompete neighbouring cells Be able to define neoantigen and know the names of the ways neoantigens can be generated -neoantigen is a tumor that can be recognized as non-self. tumors arise from self, so in order for the immune system to recognize them they must undergo a mutation that changes it somewhat significantly. Understand the difference between tumour specific antigens and tumour associated antigens tumor specific antigens are unique to and from the tumor itself tumor associated antigens are a result of the tumor existing and having an effect on other cells. for example, upregulation of signalling due to a blockage in GAP not allowing the Ras to be turned off. List the 4 methods that the immune system eliminates cancer -presentation of tumor antigens through normal MHC pathway, does not really happen -cytotoxic t-cells: can induce apoptosis through perforin and granzyme release (intrinsic), or by FasL-Fas interaction (extrinsic pathway) -antibody dependent cytotoxicity: opsonization of tumor resulting in activation of immune effector cells (NK cells) through Fc receptors -antibody dependent phagocytosis: opsonization of tumor resulting in Fc mediated phagocytosis -TIME (tumor immune microenvironment): hot (inflamed), cold (excluded), cold (ignored) Understand the differences between tumour immune microenvironment classifications and how TIL count generally impacts prognosis TIL (tumor infiltrating lymphocytes): when patients have high levels of TILs they generally are associated with higher survival statistics Understand the process of tumour immunoediting subpopulations of the tumour with higher fitness will be selected for, tumor immunoediting is the process by which the tumor continues to mutate and divide in subpopulations in order to evade death and detection Be familiar with the example mechanisms of tumor immune escape that were presented in lecture -low immunogenicity: no molecules to stimulate an immune response -tumor treated as self: tumor is not recognized as non-self and thus does not initiate an immune response -antigenic modulation: tumors that have lost their immunogenic antigens will not be eliminated by T cells -tumor induced immune suppression: some tumors can secrete factors that inhibit T cells -tumor induced privileged site: cold (excluded), physical barrier separating the tumor from the immune system *****disrupting the MHC loading pathway******** Be able to discuss CTLA-4 and PD-1/L1 immune checkpoint blockade targets and why these are good targets for therapeutic antibody treatment CTLA-4: causes the inhibition of T-cell activation, inhibiting CTLA-4 would be inhibiting an inhibitor PD-1/L1: special thing the tumor does to tell a T-cell to not be concerned about it. The PD-L1 is on the tumor, and it binds to PD-1 on the T-cell. an antibody could be used to block the binding sites on both the sites, resulting in the tumor cell being unable to calm the T-cell down. Be familiar with the general process of ACT take out a fragment of the tumor covered in T-cells, then isolate some of the T-cells on pieces of the tumor, then further isolate just the T-cells, then from those isolate the T-cells that are specific to the tumor (some could've just been there not doing anything), and expand the specific T-cells, then implant them back into the host Know what a CAR-T cell is and be familiar with the structure of the chimeric antigen receptor -great for treating cancer, they don't need MHC to activate T-cells, very specific not many side effects -SRUCTEUEr Understand the applications of radio-conjugated antibodies for treatment and diagnostics of cancer allows for the specific delivery of a radionucleotide to a target tumor cell, allows for targeted application of radiation