Innate and Adaptive Immunity Flashcards
What is immunity
- Immunity: Ability to ward off disease caused by microbes or their products and to protect against environmental agents
- Susceptibility: Lack of resistance to a disease, lack of immunity
What is innate vs adaptive immunity
Innate:
- Fast, non-specific, lack of immune memory, basic immunity, recognises foreign antigens that are highly conserved over time
- Specificity: Different microbes respond to identical mannose receptors
- Receptors: Encoded in germ-line, limited diversity, TLR are able to recognise LPS in cell wall of gram-negative bacteria and, once bound, activate release of inflammatory cytokines
- Distribution of Receptors: Non-clonal, identical receptors on all cells of same lineage
- Discrimination: Yes, host cells are not recognised or they may express molecules that prevent innate immune responses
Adaptive:
- Specificity: For structural detail of microbial molecules (antigens), may recognise non-microbial antigens, different microbes have distinct antibody molecules
- Receptors: Encoded by genes produced by somatic recombination of gene segments, greater diversity
- Distribution of Receptors: Clones of lymphocytes with distinct specificities express different receptors
- Discrimination: Yes, based on selection against self-reactive lymphocytes, may be imperfect (give rise to autoimmunity)
- Leukocytes coordinate efforts in controlling infections in the second and third lines of immune defence (high WBC = bacterial infection, low WBC = viral infection)
Provide an overview of the body’s lines of defences
First Line:
- Innate, keep pathogens on the outside or neutralise them before infection begins
- Skin, mucous membranes, and antimicrobial substances
Second Line:
- Innate, slow or contain infections when first-line defences fail
- Proteins (inflammation), fever (cytokine activity) and phagocytes / natural killer (NK) cells (attack / destroy infected cells)
Third Line:
- Adaptive, include lymphocytes that target specific pathogens for destruction when the second-line defences don’t contain infections
- It includes a memory component that allows the body to more effectively respond to that same pathogen in the future
Describe first line of defence (skin and mucous membranes - physical)
Skin:
- Dermis (inner, thicker, tightly packed protective keratin)
- Epidermis (outer, thin, direct contact with environment)
- Periodic shedding and dryness creates a formidable barrier
- Endothelial cells aren’t tightly packed, allow defensive cells to move from blood to tissue (inflammation)
Cilia:
- Mucous-coated hairs, filter inhaled air, respiratory and gastrointestinal tracts
- Ciliary Escalator: Propel inhaled dust and microorganisms upward toward throat, coughing and sneezing speed up escalator
Mucous Membranes:
- Epithelial layer and underlying connective tissue, secretes mucous
- Mucous: Slightly viscous (thick) glycoprotein produced by goblet cells, prevents tract from drying out,
Lacrimal Apparatus:
- Group of structures that manufactures and drains tears, continual washing action, excess tears dilute and wash away the irritating substance or microorganisms before infection can occur
Saliva:
- Dilutes microorganisms and wash them from surface of teeth / mouth, prevents colonisation of microbes
Urine:
- Cleansing of the urethra, prevents colonisation in genitourinary tract.
Vaginal Secretions:
- Move microorganisms out of the female body
Peristalsis, Defecation, Vomiting, Diarrhoea:
- Expel microbes, coordinated contractions that propel food along GI tract.
- In response to microbial toxins, muscles of GI tract contract vigorously, resulting in vomiting / diarrhoea
Describe first line of defence (skin and mucous membranes - chemical)
Sebum:
- Sebaceous glands of skin
- Prevents hair from drying and becoming brittle, protective film over surface of skin
- Lowers pH (3-5) of skin
Perspiration (Sweat):
- Helps maintain body temperature, eliminates certain wastes, and flushes microorganisms from skin
Lysozyme:
- Enzyme, breaks down cell walls of gram-positive bacteria
- Breaks chemical bonds on peptidoglycan
- Found in tears, saliva, nasal secretions, tissue fluids, and urine
Saliva:
- Contains salivary amylase and other substances (lysozyme, urea, and uric acid) that inhibit microbial growth
- Slightly acidic pH
Gastric Juice:
- Mixture of HCl, enzymes, and mucus, high acidity destroys bacteria / bacterial toxins
Vaginal Secretions:
- Glycogen is broken down into lactic acid, creates acidic pH, cervical mucous (antimicrobial activity)
Urine:
- Acidic pH (average 6) that inhibits microbes
What is normal microbiota and innate immunity
- Normal Microbiota: Compete with pathogens via microbial antagonism, produce substances harmful to pathogens, alter conditions that affect pathogen survival,
- Commensalism: One organism benefits while the other (host) is unharmed
- Probiotics: Live microbial cultures applied to or ingested that are intended to exert a beneficial effect
What is the lymphatic system
- Lymph fluid and lymphatic vessels, a number of structures and organs containing lymphoid tissue
- Fluid circulating between tissue cells (interstitial fluid) is picked up by lymphatic capillaries
- Lymphoid Tissue: Large numbers of lymphocytes, including T cells, B cells, and phagocytic cells that participate in immune responses
- Scattered throughout the mucous membranes that line GI, respiratory, urinary, and reproductive tracts, protect against microbes that are ingested or inhaled
Describe second line of defence (defensive cells)
- Blood: Consists of fluid (plasma) and formed elements, include erythrocytes, leukocytes and platelets
- Hematopoiesis: Process in which formed elements are produced in red bone marrow by stem cells
- Innate Cells: First cells to be recruited to site of infection
- Macrophage and dendritic cells, provide a link between innate immunity and adaptive immunity
Provide an overview of second line of defence (receptors and pathways)
- Aim: To elicit innate antimicrobial and inflammatory responses and initiate adaptive immunity for the control or elimination of infection
- Activation: Innate response is activated by protein receptors in the plasma membranes of defensive cells
- Intersection: The innate immune system is at the intersection of several pathways that influence the balance between health and disease, NOD and TLR
Describe second line of defence (pathways)
- Pathways: Five major pathways for innate immunity in mammalian cells
- Complement pathway
- TLR pathway
- NOD-like receptor (NLR) pathway
- RIG-like receptor (RLR) pathway
- C-type lectin receptor pathway
What is the complement system
Function
- The body produces certain antimicrobial substances, a final component of the second line of defence
- Completes or enhances cells of immune system in destroying microbes
Proteins Produced
- Interferons: Induce cells to produce antiviral proteins (prevent replication), activate neutrophils / macrophages
- IBPs: Transport and store iron, depriving most pathogens of the available iron
- AMPs: Inhibit cell wall synthesis, form pores in plasma membranes, and destroy DNA and RNA.
Pathways
- Three pathways which lead to inflammation / cytolysis (C3a + C5a) opsonisation (C3b, enhances phagocytosis)
- Classical: Antigen antibody reaction,
- Alternative: Contact between certain complement proteins and a pathogen, no antibodies
- Lectin: Lectin binds to mannose on surface of a microbe
Describe second line of defence (phagocytes)
- Phagocytosis: Ingestion of a microorganism by a cell, clearing of debris
- Phagocytes: Cells that perform phagocytosis, WBC and WBC derivatives
- Function: Granulocytes (neutrophils, basophils, eosinophils) and monocytes migrate to the infected area.
- They leave the blood and migrate to tissues where they enlarge and develop into roaming macrophages
- There are also fixed macrophages which are residents in certain tissues and organs of the body
Describe pathogens that evade phagocytes and how
- Inhibit adherence (M protein capsules) include S. pyogenes and S. pneumoniae
- Kill phagocytes (Leukocidins) include S. aureus
- Lyse phagocytes (membrane attack complex) include Listeria monocytogenes
- Escape phagosome includes Shigella and Rickettsia
- Prevent phagosome-lysosome fusion includes HIV and Mycobacterium tuberculosis
- Survive in phagolysosome include Coxiella burnettii
Describe adaptive immunity
- Characteristics: Slow initial response to a first-time antigen exposure, more rapid and robust response during subsequent exposures secondary to immune memory, large diversity of antigen-specific responses
- Specificity: Refers to the adaptive immune system’s ability to target specific pathogens,
- Memory: Refers to its ability to quickly respond to pathogens to which it has previously been exposed
- Dual Nature: Humoral immunity (circulating antibodies) and cell-mediated immunity
Provide a brief overview of humoral immunity
- Humoral: Immune actions in extracellular fluids, synthesising antibodies (immunoglobulins)
- Variety of functions involved in eradicating infectious agents
- B Cells: B lymphocytes, immunoglobulins corresponding to specific antigens coat surfaces of B cells, production and maturation in the red bone marrow, found in blood and lymphoid organs
- Antibodies: Secreted by plasma cells or attached to B cells, recognise and bind to a specific antigen, antigen binding sights vary (valence), least two identical antigen-binding sites bind to identical epitopes
Describe structure of antibodies
- Immunoglobulin (Ig), two light and two heavy chains that form aY-shape, trunk is theconstant fragment (Fc)
- Two branches areantigen-binding fragments (Fab), disulphide bonds
- Fc: Constant region (contains carboxy terminal and various carbohydrate side chains) and is important in both complement factor binding and determining theisotopeof the immunoglobulin
- IgM, IgD, IgE, IgG, IgA
- Fab: Contains two antigen-binding fragments (amino terminal side) that are important in determining antigen specificity, the Ag-binding domain on the Ig bind to specific regions known as epitopes
What is BCR
- B Cell Antigen Receptor
- B cells express a clonally restricted antigen receptor
- BCR expressed on cell surface or can be secreted, BCR = Ig
Describe steps of T-dependent B cell activation
- BCR receptors recognise and attach to antigen
- Antigen is phagocytized and digested
- Antigen fragments are displayed on the B cell surface attracting a matching T helper cell
- T helper cell secretes cytokines activating the B cell
- The activated B cell begins clonal expansion, producing plasma cells and memory cells
Describe steps of T-independent B cell differentiation and activation
- Stem cells differentiate into mature B cells, each bearing surface Ig against a specific antigen
- B cell encounters its specific antigen and proliferates
- Some B cells proliferate into long-lived memory cells which at a later date can be stimulated to become antibody producing plasma cells
- Plasma cells secrete antibodies into circulation
Describe the protective mechanism of antigen-antibody complex
- Agglutination: Reduces number of infectious units to be dealt with
- Opsonisation: Coating antigen with antibody enhances phagocytes
- Activation of complement: Causes inflammation and cell lysis
- Antibody dependent cytotoxicity: Antibodies attached to target cell cause destruction of macrophages, eosinophils and NK cells
- Neutralisation: Blocks adhesion of bacteria and viruses to mucosa / blocks attachment of toxin
Provide a brief overview of cell mediated immunity
- Cell-Mediated: T lymphocytes / T cells are the basis of cellular immunity, phagocytic cells, such as macrophages or dendritic cells, process and present antigenic peptides to them
- T Cells: Critical in regulation, activation and action of adaptive immune system, stem from lymphoid lineage of hematopoietic differentiation, originate in bone marrow and mature in the thymus
- Specialised T cells with different clusters of differentiation (CD) markers on their cell surface
- The main cell types are CD4 + and CD8 + T cells
- CD4 + T Cell: Helper T cells undergo further differentiation after appropriate stimulation by antigen presenting cells (APCs), activate macrophages to kill phagocytosed microbes
- CD8 + T Cell: Cytotoxic T cells, responsible for seeking out and eliminating virus / parasite-infected cells, cancer cells andother foreign cells, eliminate reservoirs of infection
Describe T cell recognition
- T Cell Antigen Receptor (TCR): Express clonally restricted antigen receptors, expressed on cell surface, cannot bind to intact proteins, can only bind to peptide fragments presented in association with MHC
- Major Histocompatibility Complex (MHC): Collection of genes coding for MHC found on surface of all nucleated cells of body, also known as human leukocyte antigen (HLA) genes
- APCs include B cells, dendritic cells, and macrophages
- Helper T cells recognise antigens processed by APCs and presented with MHC II
- Cytotoxic T cells recognise antigens processed by all host cells and presented with MHC I
Describe T cell activation
Cytotoxic
- Abnormal antigen is presented on the cell surface of cell in association with MHC class I molecules
- Activating the T cell (with its cytokine receptors)
- Cytokines activate T helper cells and macrophages
- CTLp becomes an activated cytotoxic T lymphocyte (CTL) able to induce apoptosis of the target cell.
Helper
- APC presents antigen fragments to T helper cell, binding of the TCR to the processed antigen (first signal)
- Cells are stimulated to secrete costimulatory molecule (second signal)
- Two signals activate T cell to produce cytokines
- Proliferate and activate B cells (to produce plasma cells), CTLs, and macrophages.
Describe adaptive immunity in bacteria
- The counterpart of adaptive immunity in bacteria and archaea is the CRISPR-Cas immune system
- Ability to recognise DNA sequence of bacteriophages, help the bacteria to remember which pathogen it has been previously infected with
What is the CRISPR-Cas immune system
- Bacteria have developed a specific recognition system for detection of viruses
- Small DNA fragments from virus are incorporated into specific regions on the bacterial chromosome
- These can be transcribed to small RNAs which can be used to target viral DNA for degradation
- CRISPR Enzymes: Found in bacteria and archaea, destroy foreign DNA
- Cas9 enzyme: creates blunt ended lesions in target DNA
How do bacteriophages avoiding CRISPR-Cas activity
- A phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host
- A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island
- In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication
What are NOD
- Nucleotide binding oligomerisation domain
- Intracellular proteins
- Allow detection of intracellular bacteria, detect peptidoglycan and stimulate host responses to limit bacterial infection
What are TLR
- Toll like receptors
- Attach to various components commonly found on pathogens called PAMPs
- Located in plasma membrane / endosomes, lead to stimulation of pro-inflammatory cytokines
- TLR family of receptors includes TLR1 - TLR10 in humans
- TLR1-9, TLR11, TLR12 and TLR13 found in mice and the homolog of TLR10 in mice is a pseudogene
What are PRR
- Pattern recognition receptors
- Front line defence cells detect invading pathogens through germ-line encoded pattern recognition receptors
- Soluble and membrane bound PRRs alert mammalian immune system through extracellular and intracellular activation cascades
What are PAMPs
- Pathogen associated molecular patterns
- Shared by related groups of microorganisms, usually essential for pathogen survival
- Structures unite to cell wall components not found in mammalian cells (LPS, flagellin, LTA), ligands for host innate receptors
- LPS / LTA: Lipopolysaccharide or lipoteichoic acid components of outer membrane or cell wall respectively of gram negative bacteria
- Flagellin: Found on motile bacteria
What is the microbial recognition pathway
- Responsible for the recognition of microorganisms and endogenous host-derived ligands
- Trigger the clearance and / or killing of microorganisms, apoptotic and necrotic cell-death pathways that depend on pro-inflammatory mediators
Describe the mechanism of phagocytes
- Chemotaxis and adherence of microbe to phagocyte
- Ingestion of microbe by phagocyte
- Formation of phagosome
- Fusion of the phagosome with a lysosome to form a phagolysosome
- Digestion of ingested microbe by enzymes
- Formation of residual body containing indigestible material
- Discharge of waste materials
What is primary vs secondary exposure
- Primary: First exposure to a pathogen or vaccine, no concentration of antibody to start, primary immune response is low, slow reaction
- Secondary: Subsequent exposures result in a response that is faster and stronger as a result of the body’s memory of the first exposure, antibody / memory cells present upon exposure, high immune response and increased number of antibodies, much faster
