Immunobiology - 2024 Past Paper PDF

Introduction: Immunobiology Champa Ratnatunga Department of Microbiology Faculty of Medicine University of Peradeniya Biochemistry III module Y2S1 2024 Nov/ Dec (Amended Curriculum) Outline Overview Recall what you (used to!!) know Learn some names B...

Introduction: Immunobiology Champa Ratnatunga Department of Microbiology Faculty of Medicine University of Peradeniya Biochemistry III module Y2S1 2024 Nov/ Dec (Amended Curriculum) Outline Overview Recall what you (used to!!) know Learn some names Basic immunobiology – immune response to a pathogen Innate immunity Antigen presentation to T cells Cell mediated immunity Humoral immunity Immune memory Summary  Physiology Cells Neutrophil, Monocytes, Lymphocytes Cellular functions/ Organs actions Lymph nodes and Phagocytosis (eating), lymphatics, cytotoxicity (killing other Spleen, Peyers cells), cytokine secretion patches, BALT Anatomy/ Biochemistry Immune Physiology Plasma proteins response Physical, Chemical and Defense functional barriers molecules Skin and all mucosae, Complements, lysozymes, gastric acid, Antibodies microbiome, peristalsis, Signaling and cough/ vomit reflexes Recepetor molecules Cytokines (IFNg, TNF), Biochemistry Chemokines Cytokine-R, Antigen-R, Cell signaling Damage-R  Immune system Innate Adaptive Non-specific Antigen specific Barriers and Molecules / protective reflexes Cellular Humoral/ Humoral Cells including component molecules component microbiome Skin, mucosa, Neutrophils, Baso, Complements, tears, mucus, gut Eosin, NK cells, B and T Acute phase Antibodies microbes, cough, Mono/macro, lymphocytes proteins (Ex. CRP) vomiting Dendritic cells Structure of the immune system – Revise anatomy and Phys!!! The immune system is distributed throughout the body All tissues are under surveillance! Organs Primary lymphoid organs Bone marrow Thymus Secondary lymphoid organs Lymph-nodes (LN) Spleen Lymphoid tissue aggregates Trafficking / movement of cells occurs continuously through lymphatics and blood Each immune cell type has a specific set of functions that it performS  Cytokines A family of proteins secreted by many cells (immune, epithelial etc) Signalling molecules Affect the function of other cells Ex. Interleukins – IL1, IL6; IL2, IL12; IL4,IL10 Interferons – IFNγ, IFNα, IFNβ TNF Immune cells development, trafficking, activation, differentiation and proliferation and controlled by different cytokines Pleiotropic - each cytokine can have many different functions Redundant – one function is performed by many different cytokines Chemokines A subgroup of small cytokines. Induce other cells to move to a specified target. - chemotaxis Ex. CCR7, CXCR3 Complement cascade/ system Part of the innate immune system Activated directly by molecules on pathogens, injured cells or Ag-Ab complexes Final MAC causes lysis of cell (bacterial, viral infected cell etc) where complement was activated  Components in the Humoral immunity Cellular component B cells Plasma cells – actively antibody secreting B cells T cells –Tfh needed Molecular / humoral component Immunoglobulins (Antibodies) New names and words  Antigens A molecule able to generate an immune response Could be Peptide – most antigenic because presented on MHC molecules and able to active T cell immunity Lipid Polysaccharide Nucleic acids Bind to receptors of immune cells 1 pathogen = many antigens 1 cell = many antigens Epitopes Specific region/s of an antigen that binds to the receptor (TCR/ BCR) 1 antigen = many epitopes  CD molecules All immune cells are classified and subclassified into many groups Classified based on expression of surface molecules – These molecules were named – ‘Cluster of Differentiation’ ‘CD’ Given numbers in the order they were found Used to define cells types Many have other names as well Ex. T cells –CD3+, CD4+ or CD8+ B cells –CD19+, CD20+ Importance – 1. Identification (many types look the same on light microscopy) 2. Targeting drugs Ex. Anti B cell treatment targets CD19 Immune cell identification and function: Macrophage/ DC CD3 CD4 CD8 CD19 MHC IgD/M Macrophage T Cell B Cell  MHC- Major histocompatibility complex Found in all vertebrates In humans – ‘ Human leucocyte antigens’ / HLA MHC Class I- Present on all nucleate cells HLA-A, B,C MHC Class II- Present on Professional Antigen Presenting Cells (APCs) HLA- DR, DP, DQ Immune function is to show/ present small pieces of peptide antigens (from pathogens etc) to T cells This is what is matched between donor and recipient before an organ transplant! – Tissue type is based on Highest degree of polymorphism in human genes – HLA HLA I ->12,000 HLA class II >4857 alleles identified Each person has a unique HLA type/ Tissue type (Compare to blood type which has 3 possible alleles –A,B,O- and each person has 1 pair of genes)  Receptors Receptors (could be on cell surface or inside cell/ intracellular) help cells respond to the outside environment Immune receptors – Help identify threats (internal or external) 1. Innate receptors – Many different types of receptor on innate immune cells (neutrophils, macrophages), epithelial cells etc that identify Pathogens Or Damage – as a pattern Ex. Seeing blood means someone has been injured but does not identify the person- pattern of damage. All cells in all humans have the same receptor types. 2. Adaptive/ specific receptors T cell receptor – each T cell in the body has a unique receptor – recognizes only 1 specific antigen B cell receptor –each B cell in the body has a unique receptor – recognizes only 1 specific antigen Ex. Seeing a face means you can identify the specific person – unique to each antigen  1. Innate receptors - Pattern recognition receptors (PRRs) You don’t need to memorize these!! ❖ Cell associated PRRs– Membrane bound Intracellular Can directly recognize 1. Molecules on pathogens – Pathogen associated molecular patterns Not unique to a pathogen, but generally found on pathogens Ex. Bacterial/ fungal cell wall material 2. Molecules associated with cell damage –damage associated molecular patterns  2. Specific / Adaptive immune receptors T cells Lymphocytes that develop/ mature in the thymus = T cells All have a T cell receptor- TCR Identified by surface molecules 1. CD3 part of the TCR T cells classified into 2 main groups present on all T cells 1. CD4 T cells – T helper cells (Th) 2. CD4 TCR co-receptor 2. CD8 T cells – Cytotoxic T cells (Tc) 3. CD8 TCR co-receptor  T cell receptor (TCR - CD3) Unique About 4x1011 T cell circulate in the body Each T cell has a Unique TCR on the surface B cell receptor Each B cell has a unique BCR on the surface Secreted as antibodies when B cell is activated Components- Heavy chain – determine the subtype Antibodies (α,γ,δ,μ,η,) Attached to surface of B cells - ‘BCR’ Light chain- (λ,κ) Secreted as antibodies when B cell activated Constant region –Fc Variable region – Fv The basic immune response: Overview  Overview The immune response is one process/network of processes Acute ph……. Recognized as ………… foreign/ danger Antigen Gets passed by innate Trigger – innate (bacterium, immune system defence – virus, fungi, barrier Acute ………… parasite) defences ‘Pattern inflammation …... Recognition Receptors’ Cy………... Removal of antigen and Antigen deactivation Adaptive Adaptive immunity defence presentation – of defence against the mechanisms links innate and mechanisms SPECIFIC antigen activated. adaptive and tissue activated immunity repair ………… ………… …... …...  Immune responses to infection- what you want INDUCTIO PATHOGEN REPAIR N HOMEOSTASIS ELIMINATION MEMORY Adaptive immune cells RESISTANCE TO Pathogen load RE-INFECTION Innate cells Sterilising immunity Infection Time post infection Check break Which of the following are true/ false MHC/ HLA molecules are divided into class I and class II Adaptive immune cells include T and B lymphocytes Cytokines are signaling molecules that have one function each Cytokines are needed only for phagocyte activation in innate immunity Innate immune cells have antigen specific/ unique receptor on each cell Basic Immunobiology – the immune response to a pathogen antigen Innate immunity After barriers…  Innate immune responses to infection The initial responses to: 1. Microbes: 2. Injured tissues, dead cells: Pathogen components AND tissue damage are found together in most infections PAMP and DAMP Pathogen Associated Molecular Patterns and Damage Associated Molecular Patterns These are recognized by Pattern recognition receptors (PRRs) on innate immune cells Receptor = PRRs Ligand = PAMPs / DAMPs  Two triggers sense infection… Pathogen Associated Molecular Damage Associated Molecular Patterns Patterns Common molecules present on many Molecules that are upregulated / released bacteria/ viruses/ fungi (not specific to a during cell lysis and tissue damage that species) occurs during infectious and sterile Nucleic acids (ssRNA, dsRNA, DNA) inflammation from viruses and bacteria Proteins from bacteria (pillin, flagellin) Cell wall lipids/ carbohydrates from bacteria/ fungi Microbe invades!! Increase/ activate cytokine secretion – TNF, IL1, IL6 etc.. Activation (PRR+!) and migration of immune cells Neutrophils – phagocytosis, NETosis, degranulation Dendritic cells / Macrophages –activated!!, increase phagocytosis, migration, Ag presentation Other immune cell recruitment Synthesis of acute phase proteins and chemokines Acute inflammation- mediated by cytokines, chemokines, PGs, LTXs, etc Complement activation (by microbes) Activated DC/ M phagocytose antigens Migration to LN and Ag presentation Antigen presentation on MHC Class I/ II at local LN https://veteriankey.com/innate-immunity-the-recognition-of-invaders/  Inflammation Antigen uptake by phagocytosis and loading on to MHC Class I and II molecules – Antigen presentation -Increased by inflammation -This is how T cells ‘see’ antigens Antigen presentation to T cells Process antigen – Digestion into many peptides and activated APCs migrate to draining LN or SLO Present peptides on MCH-II (and MHC-I) to T cells T cell that SPECIFICALLY recognizes the antigen via its unique TCR receives activation signals T cell response is decided by the co-stimulatory signals received Response- proliferation, cytokine production, regulatory, anergy  Usually takes place in LNs APC must keep presenting the T cell priming peptide antigen (green blob) loaded on its HLA/ MHC molecules to many CD4 / CD8 T cells Until the specific T cell that can RECOGNIZE THIS ANTIGEN with its specific TCR is found THIS TAKES TIME!!!! Process antigen – Digestion into many peptides and activated APCs migrate to draining LN or SLO Present peptides on MCH-II (and MHC-I) to T cells T cell that SPECIFICALLY recognizes the antigen via its unique TCR receives activation signals T cell response is decided by the many other signals received Response- proliferation, cytokine production, cell activation etc  Antigen specific Peptide-MHC interaction priming, and other signals Th1 type Th2 type Outcome of CD4+ T helper Naïve CD4 T activation could be cells (Th) cell- Th0 Th17 type any of these / combination of T cells T Follicular these helper Tfh T regulatory type CD8+ T cytotoxic Naïve CD8 T cell (Tc) cell - Tc0 Cytotoxic T Directly Kill infected cells cell  Effector functions: Proliferated, differentiated antigen specific CD4 T cells secrete specific T cell responses cytokines that have specific effects on other cells – increasing specific pathways of immunity – no need to know details now. Help activated B cells class switch from IgM to IgG production Help activated B cells class switch T cell from IgM to IgE and increase eos/ priming baso/ mast cell recruitment - Allergy Pathway Help activate macrophages to of increase recruitment and differentia phagocytic killing tion depends Help recruit neutrophils and on many neutrophil mediated killing signals Help control immune response by reducing inflammation  Immune responses to infection- what you want INDUCTIO PATHOGEN REPAIR N HOMEOSTASIS ELIMINATION MEMORY Adaptive immune cells RESISTANCE TO Pathogen load RE-INFECTION Innate cells Long lived specific T/ B memory cells Adaptive cells (T / B cells) with the specific receptor able to recognize this pathogen – Clonal proliferation and effector function Sterilising immunity Infection Time post infection Check break Which of the following are true Innate immune response happens within minutes to hours of activation of PRRs Innate immune cells are able to develop immune memory – respond to the same antigen better in the future Antigen presentation on MHC-I / II molecules results in activation of naïve T cells into effector T cells Antigen presentation on MHC I/II molecules results in activation of CD4 T cells into CD8 T cells. CD4 T cells directly kill pathogen infected cells and are cytotoxic.  Germinal center reaction in LN with Tfh cell assistance More details later. for now - IgM secreted first. Later this changes to IgG secretion. - Class switching/ Figure: Isotype switching Phases of humoral immune responses , Source: Cellular and Molecular Immunology, Abbas, 9th Edition.  Class switching (heavy chain isotype switch) T cell help & cytokine signals Cytokines and other signals Results in change in antibody function - No need to know details Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011 c Elsevier  Antibody functions For now – When an antibody binds to the specific antigen it forms the Ag-Ab Complex This can complex can activate different ways of inactivating or removing pathogens as well as activating immune cells and complements to come and destroy the pathogen No need of details now. , Source: Cellular and Molecular Immunology, Abbas, 9th Edition. Check break Which of the following are true Activated T / B cells proliferate and produce new cells (daughter cells) with different specific receptors (TCR/ BCR) Effector cells that are Th1 type secrete IFNg and TNF, causing macrophage activation Cytotoxic CD8 T cells kill infected cells by secreting antibodies B cell activation by a specific antigen results in immediate secretion of IgG Antibodies are able to cause cell death of infected cells through several mechanisms Adaptive Immune memory How B and T memory cells respond faster and better when they recognize the same antigen a 2nd time. And why you only get chickenpox once!!  Immunological memory First time T/B cell meets the specific antigen – Primary immune response and formation of memory cells Memory cells (T/B)- long lived- in bone marrow, LN and circulation Do not need lots of signals for activation and proliferation If they meet same antigen again presented on MHC by APCs to T cells or binding directly to BCR Memory cells respond rapidly - activated and differentiate into effector cells Quick elimination of target antigen – Immunological memory Stronger faster response on repeated exposure – Secondary immune response This also increases the memory cell population How do we make use of this feature of the adaptive immune system for PREVENTING infections? Primary Immune response - Humoral Immune response which occurs by activation of naïve B cells when specific antigen is first recognized (encountered/ met) Takes some time to mount this immune response (7-14 days) Produces IgM antibodies first but this disappears soon. Indicates an acute infection Later during the infection/ recovery phase– class switching to IgG (or other isotypes) happens with T cell help. Memory B cells provide long lasting immunity by IgG production  Secondary Immune response- humoral Subsequent encountering of the same antigen by memory B cells produces antibodies – rapidly and in a larger quantity (higher titer) The main type of antibody is IgG due to rapid heavy chain isotype (class) switching Indicates the protective immunity May last for a longer period Primary and secondary immune response – humoral adaptive immune response Principle of Vaccination! Mechanism of long term immunity from some infections!  Immune response to Dengue © 2010 Nature Publishing Group Guzman, M. G. et al. Dengue: A continuing global threat. Nature Reviews Microbiology 8, S7–S16 (2010). Check break Which of the following are true IgG is seen only in secondary infections, never in primary infections IgM provides long lasting immunity from infections Long lived plasma cells in the bone marrow secrete IgG providing long term immunity from infections Repeated exposure to an antigen will result in death of memory cells Positive IgG indicates acute infection. Summary Watch video!!!  Physiology Cells Neutrophil, Monocytes, Lymphocytes Cellular functions/ Organs actions Lymph nodes and Phagocytosis (eating), lymphatics, cytotoxicity (killing other Spleen, Peyers cells), cytokine secretion patches, BALT Anatomy/ Biochemistry Immune Physiology Plasma proteins response Physical, Chemical and Defense functional barriers molecules Skin and all mucosae, Complements, lysozymes, gastric acid, Antibodies microbiome, peristalsis, Signaling and cough/ vomit reflexes Recepetor molecules Cytokines (IFNg, TNF), Biochemistry Chemokines Cytokine-R, Antigen-R, Cell signaling Damage-R  Immune system Innate Adaptive Non-specific Antigen specific Barriers and Molecules / protective reflexes Cellular Humoral/ Humoral Cells including component molecules component microbiome Skin, mucosa, Neutrophils, Baso, Complements, tears, mucus, gut Eosin, NK cells, B and T Acute phase Antibodies microbes, cough, Mono/macro, lymphocytes proteins (Ex. CRP) vomiting Dendritic cells