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HLTH2300 > Innate and Adaptive Immunity > Flashcards

Innate and Adaptive Immunity Flashcards

1
Q

What is immunity

A
  • 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
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2
Q

What is innate vs adaptive immunity

A

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)
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3
Q

Provide an overview of the body’s lines of defences

A

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

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4
Q

Describe first line of defence (skin and mucous membranes - physical)

A

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

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5
Q

Describe first line of defence (skin and mucous membranes - chemical)

A

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

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6
Q

What is normal microbiota and innate immunity

A
  • 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
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7
Q

What is the lymphatic system

A
  • 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
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8
Q

Describe second line of defence (defensive cells)

A
  • 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
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9
Q

Provide an overview of second line of defence (receptors and pathways)

A
  • 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
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10
Q

Describe second line of defence (pathways)

A
  • 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
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11
Q

What is the complement system

A

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
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12
Q

Describe second line of defence (phagocytes)

A
  • 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
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13
Q

Describe pathogens that evade phagocytes and how

A
  • 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
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14
Q

Describe adaptive immunity

A
  • 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
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15
Q

Provide a brief overview of humoral immunity

A
  • 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
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16
Q

Describe structure of antibodies

A
  • 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
17
Q

What is BCR

A
  • B Cell Antigen Receptor
  • B cells express a clonally restricted antigen receptor
  • BCR expressed on cell surface or can be secreted, BCR = Ig
18
Q

Describe steps of T-dependent B cell activation

A
  1. BCR receptors recognise and attach to antigen
  2. Antigen is phagocytized and digested
  3. Antigen fragments are displayed on the B cell surface attracting a matching T helper cell
  4. T helper cell secretes cytokines activating the B cell
  5. The activated B cell begins clonal expansion, producing plasma cells and memory cells
19
Q

Describe steps of T-independent B cell differentiation and activation

A
  1. Stem cells differentiate into mature B cells, each bearing surface Ig against a specific antigen
  2. B cell encounters its specific antigen and proliferates
  3. Some B cells proliferate into long-lived memory cells which at a later date can be stimulated to become antibody producing plasma cells
  4. Plasma cells secrete antibodies into circulation
20
Q

Describe the protective mechanism of antigen-antibody complex

A
  • 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
21
Q

Provide a brief overview of cell mediated immunity

A
  • 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
22
Q

Describe T cell recognition

A
  • 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
23
Q

Describe T cell activation

A

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.

24
Q

Describe adaptive immunity in bacteria

A
  • 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
25
Q

What is the CRISPR-Cas immune system

A
  • 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
26
Q

How do bacteriophages avoiding CRISPR-Cas activity

A
  • 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
27
Q

What are NOD

A
  • Nucleotide binding oligomerisation domain
  • Intracellular proteins
  • Allow detection of intracellular bacteria, detect peptidoglycan and stimulate host responses to limit bacterial infection
28
Q

What are TLR

A
  • 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
29
Q

What are PRR

A
  • 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
30
Q

What are PAMPs

A
  • 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
31
Q

What is the microbial recognition pathway

A
  • 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
32
Q

Describe the mechanism of phagocytes

A
  1. Chemotaxis and adherence of microbe to phagocyte
  2. Ingestion of microbe by phagocyte
  3. Formation of phagosome
  4. Fusion of the phagosome with a lysosome to form a phagolysosome
  5. Digestion of ingested microbe by enzymes
  6. Formation of residual body containing indigestible material
  7. Discharge of waste materials
33
Q

What is primary vs secondary exposure

A
  • 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

HLTH2300 (11 decks)

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