Host Defences Flashcards
Innate vs. adaptive defenses
Innate: properties of normal host, non-specific
- Complement, antimicrobial proteins, phagocytes, inflammation and fever
Adaptive: induced by infection, slower, specific to pathogen and antigen based
- detection and response to foreign antigens
- B cells, T cells, antigen-presenting cells (macrophages and dendritic cells)
First barriers
Mucosal linings trap bacteria and ciliated cells (ex. trachea) remove mucous and trapped bacteria
Skin
Stomach and GI pH
Microbiota - compete for attachment sites and secrete bacteriocin
Antimicrobial properties: FA, blood and lymph antimicrobial proteins, lysozyme in tears,
- AMPs make pores in bacterial membranes
Second line of defense includes
Complement system: proteins which create pores in pathogen membranes and induce lysis
Phagocytes: macrophages and neutrophils take up pathogens and digest them
Inflammation: non-specific response to toxins, pathogens and tissue damage
Complement system
Blood proteins C1-C9 complement action of antibodies by forming pores on pathogens for lysis
2 pathways of activation:
1) antibody activation from APCs
2) microbial cell wall component activation
Activation –> MAC 5b6789 (membrane attack complex) –> lysis of some gram-neg
- No effect on gram pos
Serum sensitivity test
Method of testing vulnerability of bacterium to complements
Serum with complement system inside have pathogens added and do CFU to see decline if they are complement sensitive or not
Derivation of innate cells of the immune system
Bone marrow stem cell –> myeloid precursor
Myeloid –> monocytes + granulocytes
Monocytes –> Dendritic cells and macrophages
- present in blood - when they move to tissues they differentiate
- dendritic cells also involved in adaptive immune system as APCs
Granulocytes: neutrophils and mast cells
Derivation of adaptive immune cells
Bone marrow stem cell –> lymphoid precursor
Lymphoid precursor –> B cells and T cells
T cells –> cytotoxic and helper
B cells –> memory and plasma cells
White blood cells include
Monocytes –> macrophages
- phagocytosis in blood stream, attracted to inflamed tissues
Granulocytes - eosinophils, basophils, neutrophils, mast cells
- contain granules like endosomes and lysosomes
Lymphocytes - B cells and T cells
Process of phagocytosis
1) Attachment to membrane of phagocyte
2) Enclosing pathogen inside phagosome by endocytosis
3a) Either Granules containing hydrolytic enzymes fuse to form phagolysosome
Or
3b) Production of ROS inside phagolysosome oxidizes and degrades pathogen
4) Killing and digestion of pathogen
Inflammation response signs, characteristics and mechanism
Signs: red, heat, swelling, pain
Characteristics: vasodilation and ↑ permeability for antimicrobial proteins, recruitment of immune cells, complement proteins and antibodies
Mechanism:
1) Macrophages sense bacterial presence and secrete Il-1
- Il-1 stimulates vasodilation + permeability
2) Neutrophils recruited for phagocytosis
3) Mast cells release histamine into blood stream to further inflammatory response
Mechanism of fever
Macrophages sense endotoxins (LPS) –> release cytokine Il-1
Il-1 is pyrogenic and acts on thermoregulatory part of brain to increase temp
Temp >37°C reduces growth of some pathogens, but death at 44°C
Specificity, memory and tolerance in B and T cells
Each B/T cell is specific to one antigen - this is a random process during generation of B/T cells
The immune response is faster the second exposure because initial exposure expanded the antigen-reactive cells
Immune cells should not self-recognize host cells - these are killed (or autoimmunity develops)
T cell types
Antigen presentation to T cells
Helper T cells: activate B cells (Il-4) and macrophages (TNF-a)
- APC present antigens on MHC II
- activated Helper T cells produce Il-2 –> differentiation into effector + memory T cells
Cytotoxic T cells: kill any host cells which display foreign antigens on surface
- APC present antigens on MHC I
- release granzymes and perforins –> apoptosis (good against intracellular pathogens)
MHC I vs MHC II
Major Histocompatibility Complex
MHC I: expressed by all cells and marks cells for destruction by cytotoxic T cells
MHC II: expressed by antigen presenting cells like macrophages and dendritic cells and B cells
Angry killer cells
Active helper T cells release TNF-𝛂 in response to macrophages presenting recognized antigens –> angry killer cells
Angry killer cells are macrophages with ↑ phagocytic activity and higher hydrolytic enzymes
- effective against bacterial pathogens (especially intracellular macrophage pathogens which can take over)
