ETA: INFECTIOUS DISEASES
Three key lines of defence
(1) Non-specific external barriers
● Limit the entry of microorganisms into the body
(a) Physical/mechanical barriers
● Skin (epidermis and keratinocytes), mucosal epithelia of gastrointestinal, respiratory and
urogenital tracts, cilia lining respiratory tract
(b) Chemical and environmental barriers
● pH (acidic pH of skin, stomach and vagina inhibits growth of potential pathogens)
● Microcidal action of secreted molecules (e.g. lysozyme in sweat)
(c) Biological barriers
● Commensal microbes colonising skin and GIT defend their territory and inhibit
establishment of other potentially pathogenic microbes
(2) Innate immune response
● Innate immune components are present from birth and comprises non-specific internal
defences against pathogens and are available before onset of infection
Important features of innate immunity:
(a) Always present in healthy individuals and is the critical first step in host defence against
infections
○ Block microbial invasion through epithelial barriers
○ Destroy many microbes that enter the body
○ Control and even eradicate infections
(b) Able to combat microbes immediately upon infection
(c) Instructs adaptive immune system to respond to different microbes in correspondingly
effective ways
(d) Important in clearance of dead tissues and initiation of repair after tissue damage
(e) Does not lead to lasting immunity and is not specific for any individual pathogen
(f) Phylogenetically older than adaptive immunity
Components of innate immunity
(1) White blood cells
(1A) Phagocytes
● Ingest invaders by phagocytosis
○ Travel within bloodstream, are recruited to sites of infection where they recognise
and ingest microbes that penetrate the skin or mucous membranes for
intracellular killing
● Usually motile, most have lysosomes
(a) Neutrophils
● Most numerous leukocyte (60% of peripheral blood leukocytes)
● Polymorphonuclear (PMN) cells
● Formation of pus (dead neutrophils) at site of infection
● First cells recruited to acute inflammatory sites and are very effective in killing bacteria
(b) Monocytic lineage cells
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, ● Large mononuclear cells (10% of peripheral blood leukocytes)
● During inflammatory reactions, monocytes leave circulation, enter extravascular tissues
and differentiate into macrophages
● Both monocytes and macrophages actively sample their environment by phagocytosis
and serve as scavengers to remove cellular debris
(c) Dendritic cells
● Found throughout body, predominantly areas with potential microbial entry (skin, lungs,
GIT)
● Branch-like cytoplasmic projections
● Bone marrow-derived differentiated macrophages that act as antigen-presenting cells
(APCs) to activate helper T cells, cytotoxic T cells and B cells by actively engulfing
cells/particles and displaying antigens
● Important bridge between innate and adaptive immunity
(1B) Natural Killer (NK) cells
● Large, non-phagocytic, granular lymphocytes
● Non-specific defence against abnormal (infected/malignant) host cells
● Destroy virus-infected cells before proliferation of the viruses; reduces damage to body
● Patrol the body and kill non-self cells (e.g. with missing/altered MHC proteins) while
sparing self-cells
● Release proteins that bore holes in the membranes of infected/cancerous cells and
secrete enzymes through the holes
(2) Defensive proteins
(2A) Cytokines (e.g. interferons)
● Secreted proteins that function as mediators of immune and inflammatory reactions
● Innate immunity: cytokines are produced by macrophages and NK cells
○ NK cells kill virus-infected cells and secrete the macrophage activating interferon
(IFN)
● Before certain virus-infected cells die, they secrete interferons that slow down the spread
of viruses (host cell-specific)
○ Attracts macrophages and NK cells to destroy infected cells
○ Warn uninfected neighbouring cells to take protective actions (e.g. produce
proteins that prevent viruses from replicating within cells)
(2B) Complement system
● A group of at least 20 proteins whose activities enhance the body’s other defence
mechanisms
● Once activated, they enhance both innate and adaptive immunity
● Effects:
○ Destruction of pathogen (punching holes in target cell membrane, causing lysis)
○ Enhancement of phagocytosis (attract macrophages and neutrophils to site of
infection, bind to microbe surface to better allow macrophages/neutrophils to
engulf and digest microbe)
○ Stimulation of inflammation (cause blood vessels to dilate and become more
permeable, increase blood flow to area and increased access by WBCs)
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, Inflammatory response, phagocytosis and fever
(A) Inflammatory response
● Tissue reaction that delivers mediators of host defence, circulating cells and proteins to
sites of infection and tissue damage
● Recruitment of cells (leukocytes), leakage of plasma proteins (e.g. complement) through
blood vessels and activation of these cells/proteins in extravascular tissues
○ Injured tissues and macrophages at the site release chemokines which recruit
leukocytes to site
○ Initial release of histamine and other mediators by mast cells and macrophages
causes increased local blood flow, exudation of plasma proteins, and triggering
of nerve endings
○ Signs of inflammation: redness, warmth, swelling and pain
○ Local tissue accumulation of phagocytes (neutrophils) in response to cytokines
(B) Phagocytosis
● Neutrophils destroy pathogens by phagocytosis
(C) Fever
● Combats large-scale infection
● Elevated body temperature increases activity of phagocytic leukocytes and slows
bacterial growth
● Iron deficiency accompanying fever hampers bacterial division
● Causes cells of adaptive immune system to multiply more rapidly
● Stimulates virus-infected cells to produce interferon
○ Travels to other cells and increases resistance to viral attack
○ Stimulates NK cells that destroy virus-infected cells
(3) Adaptive immune response
● Specific immune response that accounts for specificity in recognition of antigens by
functional receptors on surface of B and T lymphocytes
Important features of adaptive immunity:
(a) Involves production of antibodies against a particular pathogen or its products; develops
more slowly and provides more specialised and effective defence against infections
(b) Developed during the lifetime of an individual as an adaptation to infection with a
pathogen; results in immunological memory, which confers lifelong protective immunity to
reinfection with the same pathogen
(c) Involves B and T lymphocytes which adapt to the presence of microbial invaders
● Lymphocytes express receptors that specifically recognise antigens
● Expansion and differentiation of lymphocytes in response to microbes
(d) Functions to greatly enhance the antimicrobial mechanisms of innate immunity to
eliminate microbes
Types of adaptive immunity
(1) Humoral immunity
● Mediated by antibodies (immunoglobulins) produced by B
lymphocytes
Copyright © 2019 tonyndr
Three key lines of defence
(1) Non-specific external barriers
● Limit the entry of microorganisms into the body
(a) Physical/mechanical barriers
● Skin (epidermis and keratinocytes), mucosal epithelia of gastrointestinal, respiratory and
urogenital tracts, cilia lining respiratory tract
(b) Chemical and environmental barriers
● pH (acidic pH of skin, stomach and vagina inhibits growth of potential pathogens)
● Microcidal action of secreted molecules (e.g. lysozyme in sweat)
(c) Biological barriers
● Commensal microbes colonising skin and GIT defend their territory and inhibit
establishment of other potentially pathogenic microbes
(2) Innate immune response
● Innate immune components are present from birth and comprises non-specific internal
defences against pathogens and are available before onset of infection
Important features of innate immunity:
(a) Always present in healthy individuals and is the critical first step in host defence against
infections
○ Block microbial invasion through epithelial barriers
○ Destroy many microbes that enter the body
○ Control and even eradicate infections
(b) Able to combat microbes immediately upon infection
(c) Instructs adaptive immune system to respond to different microbes in correspondingly
effective ways
(d) Important in clearance of dead tissues and initiation of repair after tissue damage
(e) Does not lead to lasting immunity and is not specific for any individual pathogen
(f) Phylogenetically older than adaptive immunity
Components of innate immunity
(1) White blood cells
(1A) Phagocytes
● Ingest invaders by phagocytosis
○ Travel within bloodstream, are recruited to sites of infection where they recognise
and ingest microbes that penetrate the skin or mucous membranes for
intracellular killing
● Usually motile, most have lysosomes
(a) Neutrophils
● Most numerous leukocyte (60% of peripheral blood leukocytes)
● Polymorphonuclear (PMN) cells
● Formation of pus (dead neutrophils) at site of infection
● First cells recruited to acute inflammatory sites and are very effective in killing bacteria
(b) Monocytic lineage cells
Copyright © 2019 tonyndr
, ● Large mononuclear cells (10% of peripheral blood leukocytes)
● During inflammatory reactions, monocytes leave circulation, enter extravascular tissues
and differentiate into macrophages
● Both monocytes and macrophages actively sample their environment by phagocytosis
and serve as scavengers to remove cellular debris
(c) Dendritic cells
● Found throughout body, predominantly areas with potential microbial entry (skin, lungs,
GIT)
● Branch-like cytoplasmic projections
● Bone marrow-derived differentiated macrophages that act as antigen-presenting cells
(APCs) to activate helper T cells, cytotoxic T cells and B cells by actively engulfing
cells/particles and displaying antigens
● Important bridge between innate and adaptive immunity
(1B) Natural Killer (NK) cells
● Large, non-phagocytic, granular lymphocytes
● Non-specific defence against abnormal (infected/malignant) host cells
● Destroy virus-infected cells before proliferation of the viruses; reduces damage to body
● Patrol the body and kill non-self cells (e.g. with missing/altered MHC proteins) while
sparing self-cells
● Release proteins that bore holes in the membranes of infected/cancerous cells and
secrete enzymes through the holes
(2) Defensive proteins
(2A) Cytokines (e.g. interferons)
● Secreted proteins that function as mediators of immune and inflammatory reactions
● Innate immunity: cytokines are produced by macrophages and NK cells
○ NK cells kill virus-infected cells and secrete the macrophage activating interferon
(IFN)
● Before certain virus-infected cells die, they secrete interferons that slow down the spread
of viruses (host cell-specific)
○ Attracts macrophages and NK cells to destroy infected cells
○ Warn uninfected neighbouring cells to take protective actions (e.g. produce
proteins that prevent viruses from replicating within cells)
(2B) Complement system
● A group of at least 20 proteins whose activities enhance the body’s other defence
mechanisms
● Once activated, they enhance both innate and adaptive immunity
● Effects:
○ Destruction of pathogen (punching holes in target cell membrane, causing lysis)
○ Enhancement of phagocytosis (attract macrophages and neutrophils to site of
infection, bind to microbe surface to better allow macrophages/neutrophils to
engulf and digest microbe)
○ Stimulation of inflammation (cause blood vessels to dilate and become more
permeable, increase blood flow to area and increased access by WBCs)
Copyright © 2019 tonyndr
, Inflammatory response, phagocytosis and fever
(A) Inflammatory response
● Tissue reaction that delivers mediators of host defence, circulating cells and proteins to
sites of infection and tissue damage
● Recruitment of cells (leukocytes), leakage of plasma proteins (e.g. complement) through
blood vessels and activation of these cells/proteins in extravascular tissues
○ Injured tissues and macrophages at the site release chemokines which recruit
leukocytes to site
○ Initial release of histamine and other mediators by mast cells and macrophages
causes increased local blood flow, exudation of plasma proteins, and triggering
of nerve endings
○ Signs of inflammation: redness, warmth, swelling and pain
○ Local tissue accumulation of phagocytes (neutrophils) in response to cytokines
(B) Phagocytosis
● Neutrophils destroy pathogens by phagocytosis
(C) Fever
● Combats large-scale infection
● Elevated body temperature increases activity of phagocytic leukocytes and slows
bacterial growth
● Iron deficiency accompanying fever hampers bacterial division
● Causes cells of adaptive immune system to multiply more rapidly
● Stimulates virus-infected cells to produce interferon
○ Travels to other cells and increases resistance to viral attack
○ Stimulates NK cells that destroy virus-infected cells
(3) Adaptive immune response
● Specific immune response that accounts for specificity in recognition of antigens by
functional receptors on surface of B and T lymphocytes
Important features of adaptive immunity:
(a) Involves production of antibodies against a particular pathogen or its products; develops
more slowly and provides more specialised and effective defence against infections
(b) Developed during the lifetime of an individual as an adaptation to infection with a
pathogen; results in immunological memory, which confers lifelong protective immunity to
reinfection with the same pathogen
(c) Involves B and T lymphocytes which adapt to the presence of microbial invaders
● Lymphocytes express receptors that specifically recognise antigens
● Expansion and differentiation of lymphocytes in response to microbes
(d) Functions to greatly enhance the antimicrobial mechanisms of innate immunity to
eliminate microbes
Types of adaptive immunity
(1) Humoral immunity
● Mediated by antibodies (immunoglobulins) produced by B
lymphocytes
Copyright © 2019 tonyndr
