Innate Immune System (part A and B) Flashcards
Explain the overall scheme and divisions of the immune system
Describe the immune and lymphoid system
Immune system provides places (niches) for immune cell generation (hematopoiesis), maturation, residence and enable interaction between immune cells and foreign agents
Lymph system is a network of vessels draining excess body fluid from organs back to heart, immune surveillance and highways for immune cells
What are primary and secondary lymphoid organs and what are their functions
Primary lymphoid organ: bone marrow and thymus
Function: generation and maturation of immune cells
Secondary lymphoid organ: spleen, lymph nodes, Peyer’s patches, MALT
- distributed throughout body
Function: provide places for interaction between immune cells, their proliferation and to produce products e.g. antibodies + identification of microbes, inactivation, killing and removal
Describe the primary defence mechanisms in the body (1st line of defence) - BIOCHEMICAL AND PHYSICAL BARRIERS
Clue: 5 parts
Keratinized skin: lining external surface of the body
-sebaceous secretions: lactic acid and fatty acids, low pH
Mucus membranes: lining inner surface of body cavities
- mucus stops attachment of microorganisms
- Mechanical removal: coughing, sneezing, cilia
Body fluids and secretions:
- flushing action by tears, saliva and urine stop microbial growth on epithelial surfaces
Mirocidal factors –> directly damage and kill microorganisms
- acid in gastric juices, spermine and zinc in sperm, lysozyme in tears, nasal secretions and saliva
Body flora (microbiota) –> host provides env and nutrients without harm
suppress growth of potentially pathogenic microorganisms by:
- already occupying growth surface
- effectively competing for nutrients
Describe the 2 aspects of the secondary line of defence and any steps associated with it
-
Phagocytosis (engulfment by professional macrophages)
i. The phagocyte attaches to the parasite with specific receptors
ii. Pseudopodia extend out and around the parasite and internalise it
iii. Lysozymes fuse with the phagosome
iv. The various antimicrobial chemicals kill the parasite - Soluble chemical factors (destruction of microorganism)
What are the major innate immune cell types and describe their characteristics and functions
Dendritic cells:
Antigen presenting cells for T cells in the adpative immune system
Macrophages:
- Macrophages in tissues - mononuclear phagocytic system
- Long lived, contain mitochondria for energy production
- Produce many anti-microbial secretory products
- Concentrated in lung, liver, spleen and lymph nodes
Neutrophils:
- Most abundant WBC in blood, 60-70 %
- Phagocytic –> first at infection sites
- Short lived = 4 days
- No mitochondria –> energy from gylcogen stores (glycolysis enables function under anaerobic conditions)
Basophils:
Least abundant leukocyte, 0.5-1 %
- Release cytokines to produce inflammation e.g. histamine
- Produce heparin which stops clotting
- Stains dark blue with basic dyes
- Leave circulating blood and turn into mast cells
Eosinophils:
- Stain bright red with acidic dyes
- Important defence against certain parasitic worms
- Inhibits inflammatory cytokines like histamine
Where are the phagocytic cells and the polymorphonuclear cells of the innate IS produced?
Phagocytic cells
Generated in bone marrow from myeloid progenitor
- Monocotyes- derived progenitor = large macrophages
- Polymorphonuclear granulocyte = small cell (neutrophil)
Polymorphonuclear cells .
Produced in bone marrow and released into blood
> Nucleus is lobulated
- Granulocyes: neutrophils, eosinophils, basophil
- Agranulocyte: monocyte
Explain what pathogen recogntiton is by the innate immune system
Pathogen and host macrophage must come into contact –> through specific receptors
> Innate IS use germline-encoded receptors for the recognition of microbial pathogens –> few receptors
> Adpative IS use receptors generated by somatic mechanisms during development of each individual immune cell (mant different tpyes of receptors)
- Innate IS detects molecular patterns found in other organisms (eg bacteria, virus, fungi)
- Pathogens have a much shorter generation time than higher animals –> variants can arise to evade recognition or response
What are Pathogen-Associated Microbial Patterns?
Because microbes evolve rapidly, innate immunity must focus:
> on broadly expressed molecules (characteristic of microbes)
> target molecules tend to be structural elements that are common to broad classes of microbes and are unlikely to change
PAMPs = targets recognised on pathogens
- to avoid damage to ‘self’ cells and tissues, they are absolutely distinct from host proteins/molecules
- essential for physiology and survivial of the microbes –> do not change
- Ability of innate IS to discriminate between self and non-self is virtually perfect
What are pathogen recognition receptors (PRR) and explain one in detail
Used by phagocytes to detect PAMPs
- Various types –> both extracellular (on surface of cell membrane) and intracellular (in phagosome)
Direct detection through receptor –> Toll like receptor (TLR)
Toll like receptor (TLR)
- Found on surface of lymphocytes, neutrophils, basophils, macrophages and dendritic cells
- 11 different types and specific to one type of PAMP (activates innate and adaptive immune system)
- Interaction between TLR-PAMP activate secretion of cytokines
- Identify foreigness for phagocytosis and destruction
What is the complement system and what effects does it have on antimicrobials?
CLUE: regarding 2nd part of the question, use terminology C3b, C3a/C5a, C5b
CS is made up up 30 proteins, major called C1-C9, secreted by liver in an inactive state and circulate in blood
- Enhance/complements the ability antibodies and phagocytic cells bind to and eliminate pathogens –> can also directly kill foreign cells
Various ways complement can be activated:
A) Classic Pathway: antigen-antibody complexes (adaptive IS)
B) Alternative Parhway: select molecules on bacterial cell wall (innate IS)
C) Acute phase proteins/lectin pathway: CRP and MBL (innate IS)
Activities of the Complement Components
Activation of central C3 protein:
- C3b coat microbes in immediate area and results in ehances phagocytosis (opsinization)
- C3a/C5a cause mast cells to degranulate –> release pro-inflam cytokines = increased vascular permeability (attract other polymorphs from blood into tissue like eosinophils, basophils, mast cells)
- C5b activates components at site of C3b/C5b attachment –> membrane attach complex – creates channels across membrane, resulting in cell lysis
What are soluble factors? Provide two or three examples.
Clue: APP, C, I
1) Acute phase proteins:
- Increase dramatically in conc in response to infection, inflammation and tissue injury
- They recognise and bind to PAMPs
- Examples: C-reactive protein, also recruit complement
2) Cytokines
- Small protein secreted by many cells e.g. lymphocytes, APC, fibroblasts, endothelial cells, monocytes
- Many are called interleukins and used by the immune cells to control process and communicate
Functions:
> Stimulate cell growth and differentiation
> Simulate proliferation of progenitor blood cells in bone M
> Regulate immune cell activity
> Drives hypersensitivity reactions and inflammation
> Imbalances in cytokine production can lead to diseases
3) Interferons (IFN)
Antimicrobial cytokines
- Three types: IFN-a, IFN-b, IFN-y
- Produced by immune and non-immune cells: B-cells, macrophages, fibroblasts, NK cells
- Protect uninfected cells from viruses
- Also induced by tumours and protectiont against other intracellullar parasites including bacteria and protozoa
How do interferons stop viruses from infecting cells
IFN a/b is produced when a cell is infected by a virus
> IFN binds to uninfected cell
>IFN induces synthesis of antiviral molecules
>Cell remains uninfected –> antiviral state develops in a few hours, lasts for a day or two
What is the general features and functions of the acute inflammatory reponse?
Normal body response to injury, irritation, microbial infection or toxin
RESULTS IN A SERIES OF EVENTS
- Physiological level: redness, heat, swelling, pain
- Cellular level: increased capillary diameter (vasodilation), increased blood flow, increased capillary permeability, escape of plasma proteins (antibodies, complement, fibrinogen)
- Escape of leukocytes and accumulation at site
Describe mechanisms of intracellular killing by phagocytic cells (3 mechanisms)
Once pathogen is phagocytosed, fusion of lysosome result in phagosome –> secretion of many antimicrobial proteins and chemicals to kill and break down
Oxidative mechanisms (by macrophages and PMN)
- Production of reactive oxygen intermediates (ROI)
- Reactions that reduce oxygen to water producing ROI in the process e.g. superoxide ions, hydrogen peroxide
- Extremely toxic –> damage cell wall strucutures and proteins
- Reduction in PH contributes to damage and acitivity of proteins
Non-oxidative mexhanisms (by macrophages and PMN)
- Function under anaerobic conditions
- Lysosomes fuse with phagosome and release contents
- Cathespin G - enzyme, damages microbial surfaces
- Lysozyme- enzyme, digests proteoglycans of cell wall
Nitric Oxide (NO)
- Major macrophage product
- Important cell signalling and potent vasodilator
- Short-lived, colourless gas
- Final step is biochemcial breakdown of killed organism
> acid hydrolases - enzymes e.g. proteases, DNAses
