Immunology: Immune response to infection/ Primary immune deficiencies Part 1 Flashcards
Summarise the overall normal protective immune response
- Pathogen passes through the constitutive barriers
- Pathogen either infects intracellularly (eg virus) or extracellularly (Eg staphylococcus Aureus)
- Innate immune response: Neutrophils engulf pathogens then die. Macrophages are already present and engulf pathogens similarly, without dying. NK cells engulf infected cells (ie cells with reduced expression of HLA) (targeting intracellular pathogens).
- Innate-adaptive transition: mediated by dendritic cells, they engulf the pathogen, processes it, then move to lymph nodes and presents antigens to CD4 T cells (Helper cells).
- Adaptive immune response: CD4 helper cells recruit CD8 (Cytotoxic) T cells. CD8 T cells kill infected cells presenting MHC class I.
- (More adaptive immune response) B-cells produce IgM early after binding to pathogen. CD4 helper cells once primed, cause B-cells to proliferate, undergo affinity maturation and mature into plasma cells that produced IgG, IgA and IgE. Immune complexes formed by these Igs and the extracellular pathogen activate the complement pathway and a can also be engulfed by macrophages and NK cells.
- Complement pathway: primarily causes perforation of the membrane of pathogens after the formation of a membrane attack complex.
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- Pathogen passes through the constitutive barriers (Either skin or a mucosal membrane)
- Pathogen either infects intracellularly (eg virus) or extracellularly (Eg staphylococcus Aureus)
- Innate immune response: Neutrophils engulf pathogens (using eg PAMPS) then die. Macrophages are already present and engulf pathogens similarly, without dying. NK cells engulf infected cells (ie cells with reduced expression of HLA) (targeting intracellular pathogens).
- Innate-adaptive transition: mediated by dendritic cells, they engulf the pathogen, processes it, then move to lymph nodes and presents antigens to CD4 T cells (Helper cells).
- Adaptive immune response: CD4 helper cells recruit CD8 (Cytotoxic) T cells. CD8 T cells kill infected cells presenting MHC class I.
- (More adaptive immune response) B-cells produce IgM early after binding to pathogen. CD4 helper cells once primed, cause B-cells to proliferate, undergo affinity maturation and mature into plasma cells that produced IgG, IgA and IgE. Immune complexes formed by these Igs and the extracellular pathogen activate the complement pathway and a can also be engulfed by macrophages and NK cells.
- Complement pathway: primarily causes perforation of the membrane of pathogens after the formation of a membrane attack complex.
Outline the physical barriers to infection.
-Skin -Mucosal membranes (eg gastrointestinal tract) that can contain commensal bacteria
Describe the cells of the innate immune system overall
- Polymorphonuclear cells: neutrophils, eosinophils, basophils: //rapidly migrate to sites of injury/infection
- Monocytes and macrophages: //can process antigens of pathogens and present them.
- Natural killer cells: //Lymphocytes that kill all cells it fails to recognise, and are down-regulated by self-HLA molecules that are recognised by inhibitory receptors.
- Dendritic cells: //engulf pathogen, subsequently mature, move to the lymph nodes and present antigens to CD4 helper T cells. Mediates the transition from innate to adaptive immunity.
Describe the cells of the adaptive immune system overall
-CD4+ (Helper) T cells: recognises antigens from extracellular proteins presented on HLA class II molecules. ‘Helps’ development of full B-cell response and some CD8+ responses -CD8+ (Cytotoxic) T cells: Recognises peptides (usually derived from intracellular organisms) presented on HLA class I molecules. Directly kills cells. -B-cells: lymphocytes that encounters antigens and produce IgM. Subsequently undergo activation by CD4+ cells, causing proliferation, somatic hypermutation, affinity maturation and the B-cells to start producing IgG, IgA and IgE.
Summarise the complement system
- Made of 3 main pathways: Classical, MBL and alternative pathways that converge on C3 convertase
- A system of 20 tightly regulated proteins, produced by liver, circulating in an inactive form. When triggered, a chemical cascade occurs, causing activation of proteins, leading to an rapid, amplified response (Kinda like coagulation)
- Classical pathway: C1, C4, C2. Depends on adaptive immune response
- Mannose-binding lectin (MBL) pathway: cell surface carbohydrates (C4, C2). Not dependent on adaptive IR.
- Alternative pathway: Bacterial cell wall. Not dependent.
- Final common pathway (C5-C9) leads to formation of the membrane attack complex (MAC). This MAC makes holes in the membranes of pathogens.
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-Other effects: –increased vascular permeability –Immune complexes become more soluble –Pathogens are opsonised (like condiments on food, improve phagocytosis).
Describe the function of chemokines
- A type of cytokine that attracts cells (with receptors for that cytokine)
- Examples of chemokines: CCL19 and CCL21, that direct dendritic cells to the lymph nodes once they have engulfed a pathogen (Dendritic cells have CCR7, chemokine receptor).
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-(Cellular damage and bacterial products trigger the local production of inflammatory cytokines and chemokines. Chemokines can attract phagocytes [although macrophages are already present at peripheral sites]).
Describe the function of cytokines
-In general cytokines are chemical messenger proteins that are secreted by cells (mainly immune cells) to affect other cells. They have an immunomodulatory function.
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- Examples of cytokines: IL-2, IL-6, TNF-α
- (eg Cellular damage and bacterial products trigger the local production of inflammatory cytokines and chemokines)
Describe the characteristics of the skin that prevent infection
- Tightly packed keratinised cells: acts as a physical barrier.
- Low pH and low oxygen tension: acidic and hypoxic environment prevents pathogen survival.
- Sebaceous glands:
- Secrete hydrophobic oils repel water and micro organisms.
- Secrete lysozyme, which destroys cell walls of pathogens
- Secrete ammonia and defensins, substances with antimicorbial properties
Describe the characteristics of the mucosal membranes that prevent infection
-Mucous: physical barrier that traps pathogens. -Mucous also contains secretory IgA, that prevents bacteria and viruses attaching to and penetrating epithelial cells. -Mucous also contains lysozyme and antimicrobial peptides that kill pathogens -Mucous also contains lactoferrin, which starves invading bacteria of iron. -Cilia: –Directly traps pathogens and assists in the movement and clearance of mucous
Describe how commensal bacteria prevents infections
-They compete with pathogenic micro organisms for scarce resources -They produce fatty acids and bactericidins that inhibit the growth of many pathogens
Give some examples of intracellular pathogens
-Viruses -Mycobacteria -Some forms of yeast
Give some examples of extracellular pathogens
-Staphylococcus Aureus -Bacillus Anthracis -Enterotoxigenic Escherichia Coli
List the soluble components of the innate immune system.
-Complement -Acute phase proteins -Cytokines and chemokines
Outline the characteristics of cells of the innate immune system
-Express receptors that allow them to detect and move to sites of infection -Pattern recognition receptors: detect pathogens at site of infection -Phagocytic capacity: allows them to engulf pathogens -Secretion of cytokines and chemokines to regulate immune response
Explain the role of polymorphonuclear cells in the innate immune response
-Migrate rapidly to the site of injury -Capable of phagocytosis by oxidative and non-oxidative killing -Release enzymes, histamine and inflammatory mediators (Granules) -Secrete cytokines and chemokines -Recognises pathogens with its pattern recognition receptors -Recognises immune complexes with its Fc receptors (for Ig). -Recognises inflammation and injury with its cytokine/chemokine receptors
Explain the role of monocytes and macrophages in the innate immune response
-Usually reside readily at the site of injury -Capable of phagocytosis by oxidative and non-oxidative killing -Presents processed antigens to T cells once phagocytosis has occurred. -Secretes cytokines and chemokines -Recognises pathogens with its pattern recognition receptors -Recognises immune complexes with its Fc receptors (For Ig). -Recognises inflammation and injury with its cytokine/chemokine receptors [Monocytes move into peripheral tissues and are referred to macrophages, with different names depending on where they are, eg Liver: Kuppfer cells, kidney: mesangial cells]
