By Adam Hollingworth
Immunology
Table
of
Contents
Immunology
..........................................................................................................................................................
1
Immunity
................................................................................................................................................................
2
Innate
Immunity
..................................................................................................................................................
2
Soluble
Factors
oF
Innate
Immune
System
.............................................................................................................
2
Cellular
Factors
of
Innate
System
...............................................................................................................................
3
Complement
..........................................................................................................................................................
4
Adaptive
Immunity
.............................................................................................................................................
6
Subclassification
of
Adaptive
immunity
..................................................................................................................
6
B
lymphocytes
...................................................................................................................................................................
6
T
Lymphocytes
..................................................................................................................................................................
7
Soluble
Factors
of
Adaptive
System
..............................................................................................................
8
Immunoglobulins
(Ig)
....................................................................................................................................................
8
Tumor
Necrosis
Factor
(TNF-‐α)
...............................................................................................................................
10
Cytokines
.........................................................................................................................................................................
10
Interferons
.........................................................................................................................................................................................
11
Cellular
Factors
of
Adaptive
System
............................................................................................................
11
Macrophagues
................................................................................................................................................................
11
T-‐Lymphocytes
..............................................................................................................................................................
12
B
Lymphocytes
...............................................................................................................................................................
12
Dendritic
Cells
................................................................................................................................................................
12
Overview
of
Immune
Response
....................................................................................................................
12
Factors
Determining
Immune
Response
..............................................................................................................
12
Primary
Response
........................................................................................................................................................
13
Secondary
Response
....................................................................................................................................................
13
Tolerance
.........................................................................................................................................................................
13
Anaesthesia
on
Immune
Functions
.............................................................................................................
13
Histocompatibility
Molecules
........................................................................................................................
13
Systemic
Inflammatory
Response
Syndrome
..........................................................................................
14
Definitions
.......................................................................................................................................................................
14
Causes
...............................................................................................................................................................................
14
Pathophysiology
............................................................................................................................................................
15
Hypersensitivity
Reactions
............................................................................................................................
17
Classifications
................................................................................................................................................................
17
Type
I
(immediate)
Hypersensitivity
.....................................................................................................................
18
Type
II
(Antibody
Mediated)
Hypersensitivity
...................................................................................................
21
Type
III
(Immune
Complex-‐Mediated)
Hypersensitivity
................................................................................
22
Type
IV
(cell
mediated)
Hypersensitivity
.............................................................................................................
23
Delayed
Type
Hypersensitivity
.................................................................................................................................................
24
T
Cell
Mediated
Cytotoxicity
.......................................................................................................................................................
25
Transplant
Rejection
........................................................................................................................................
26
Recognising
Allografts
–
(Sensitisation
Phase)
..................................................................................................
26
Graft
Destruction
Phase
..............................................................................................................................................
27
Types
of
Rejection
........................................................................................................................................................
27
Transplant
Haematopoietic
Cells
............................................................................................................................
28
Immunology - 1
, By Adam Hollingworth
Immunity
• Innate =
o mechanisms present & already synthesised prior to infection
o physical, biochemical & cellular factors (limited)
o static resistance, no memory
! specifically good at working against microbes
• Adaptive (aka acquired):
o = microbes stimulate mechanisms which are capable of recognising non-microbial substances eg
antigens
o more powerful, 2nd line defense
o memory, with subsequent enhanced response
o immune response refers to adaptive
Innate Immunity
• 1st line defence
• main components:
o Physical defences:
! epithelial barriers
! commensural flora, gastric fluid acididy, fever, lung surfactant
o biochemical defences:
! soluble factors:
• lysosumes
• acute phase reactants eg CRP
• complement
• fibronectin
• interferon
o cellular:
! phagocytic cells eg neutrophil & MPs
! NK (natural killer) cells
Soluble
Factors
oF
Innate
Immune
System
1. Lysozymes
• Distributed widely in many secretions
• Act by cleaving bacterial cell wall proteoglycans
2. Fibronectin
• Family of closely related glycoproteins
• Synthesised by endothelial cells & fibroblasts
• Actions:
o Non specific opsonisation
o Facilitation of phagocytosis
o Wound healing & tissue repair
• Levels ↓ed by: major burns, surgery, trauma, DIC
3. Complement
• see separate section below
4. Interferons
• From virally infected cells & malignant cells
• Transmit information to adjacent cells
• Activate NK cells ⇒ ↑cytotoxic action
Immunology - 2
, By Adam Hollingworth
5. Acute Phase Reactants
• Eg CRP:
o Recognises & binds wade variety of bacteria & fungi
o Acts as an opsonin ie ↑phagocytosis & complements action
Cellular
Factors
of
Innate
System
Natural Killer Cells
• =10-15% blood lymphocytes
• non thymic
• aka large granular lymphoctytes
• don’t have TLRs (no antigenic surface markers of T/B cells)
• part of innate immune system – but are regulated by T cells ∴ also role in adaptive immunity
• Different cytokines/interferons regulate NK cells – proliferate or kill
• role to kill with no presensitisation:
o tumour cells
o virally infected cells
o some normal cells
• activity mediated by balance of activating & inhibitory receptors:
o inhibition by recognition of self class I MHC molecules
! = killer inhibitory receptors
• all nucleated normal cells express class I MHC
! virally infected cells ↓s expression of class I MHC ⇒ NK cell lysis (in conjunction with
activating receptors
• NKs also secrete cytokines:
o IFN-y ⇒
! activate macrophague
! differentiate CD4+ cells ⇒ TH1 cells
o TNF
o Granulocyte macrophague colong stim factor (GM-CSF)
Neutrophils
• 80-90% of circulating polymorphs
• contain: lysozymes, phagosomes, ingested organisms, phagolysozomes
• are able to penetrate endothelial surface under influence of chemotactic factors
Esinophils
• can phagocytose
• can degranulate adjacent large foreign bodies (which too large for phagocytosis) eg worms
• attracted by eosinophil chemotactic factor
• attach to Ig’s & foreign particles
• release:
o major basic protein
o eosinophil cationic protein
o anti-inflam enzymes
• may have role in immune down regulation
Basophils & Mast Cells
• limited no in circulation
• predominantly assoc with epithelial cells esp mast cells
• may play role in immunity to parasitic infections ie ↑ed response
Phagocytes
• Phagocytes recruited to site of infection ⇒ inflam
• Phagocytes recognise microbes by receptors for:
o mannose residues not produced by host
cells
Immunology - 3
Immunology
Table
of
Contents
Immunology
..........................................................................................................................................................
1
Immunity
................................................................................................................................................................
2
Innate
Immunity
..................................................................................................................................................
2
Soluble
Factors
oF
Innate
Immune
System
.............................................................................................................
2
Cellular
Factors
of
Innate
System
...............................................................................................................................
3
Complement
..........................................................................................................................................................
4
Adaptive
Immunity
.............................................................................................................................................
6
Subclassification
of
Adaptive
immunity
..................................................................................................................
6
B
lymphocytes
...................................................................................................................................................................
6
T
Lymphocytes
..................................................................................................................................................................
7
Soluble
Factors
of
Adaptive
System
..............................................................................................................
8
Immunoglobulins
(Ig)
....................................................................................................................................................
8
Tumor
Necrosis
Factor
(TNF-‐α)
...............................................................................................................................
10
Cytokines
.........................................................................................................................................................................
10
Interferons
.........................................................................................................................................................................................
11
Cellular
Factors
of
Adaptive
System
............................................................................................................
11
Macrophagues
................................................................................................................................................................
11
T-‐Lymphocytes
..............................................................................................................................................................
12
B
Lymphocytes
...............................................................................................................................................................
12
Dendritic
Cells
................................................................................................................................................................
12
Overview
of
Immune
Response
....................................................................................................................
12
Factors
Determining
Immune
Response
..............................................................................................................
12
Primary
Response
........................................................................................................................................................
13
Secondary
Response
....................................................................................................................................................
13
Tolerance
.........................................................................................................................................................................
13
Anaesthesia
on
Immune
Functions
.............................................................................................................
13
Histocompatibility
Molecules
........................................................................................................................
13
Systemic
Inflammatory
Response
Syndrome
..........................................................................................
14
Definitions
.......................................................................................................................................................................
14
Causes
...............................................................................................................................................................................
14
Pathophysiology
............................................................................................................................................................
15
Hypersensitivity
Reactions
............................................................................................................................
17
Classifications
................................................................................................................................................................
17
Type
I
(immediate)
Hypersensitivity
.....................................................................................................................
18
Type
II
(Antibody
Mediated)
Hypersensitivity
...................................................................................................
21
Type
III
(Immune
Complex-‐Mediated)
Hypersensitivity
................................................................................
22
Type
IV
(cell
mediated)
Hypersensitivity
.............................................................................................................
23
Delayed
Type
Hypersensitivity
.................................................................................................................................................
24
T
Cell
Mediated
Cytotoxicity
.......................................................................................................................................................
25
Transplant
Rejection
........................................................................................................................................
26
Recognising
Allografts
–
(Sensitisation
Phase)
..................................................................................................
26
Graft
Destruction
Phase
..............................................................................................................................................
27
Types
of
Rejection
........................................................................................................................................................
27
Transplant
Haematopoietic
Cells
............................................................................................................................
28
Immunology - 1
, By Adam Hollingworth
Immunity
• Innate =
o mechanisms present & already synthesised prior to infection
o physical, biochemical & cellular factors (limited)
o static resistance, no memory
! specifically good at working against microbes
• Adaptive (aka acquired):
o = microbes stimulate mechanisms which are capable of recognising non-microbial substances eg
antigens
o more powerful, 2nd line defense
o memory, with subsequent enhanced response
o immune response refers to adaptive
Innate Immunity
• 1st line defence
• main components:
o Physical defences:
! epithelial barriers
! commensural flora, gastric fluid acididy, fever, lung surfactant
o biochemical defences:
! soluble factors:
• lysosumes
• acute phase reactants eg CRP
• complement
• fibronectin
• interferon
o cellular:
! phagocytic cells eg neutrophil & MPs
! NK (natural killer) cells
Soluble
Factors
oF
Innate
Immune
System
1. Lysozymes
• Distributed widely in many secretions
• Act by cleaving bacterial cell wall proteoglycans
2. Fibronectin
• Family of closely related glycoproteins
• Synthesised by endothelial cells & fibroblasts
• Actions:
o Non specific opsonisation
o Facilitation of phagocytosis
o Wound healing & tissue repair
• Levels ↓ed by: major burns, surgery, trauma, DIC
3. Complement
• see separate section below
4. Interferons
• From virally infected cells & malignant cells
• Transmit information to adjacent cells
• Activate NK cells ⇒ ↑cytotoxic action
Immunology - 2
, By Adam Hollingworth
5. Acute Phase Reactants
• Eg CRP:
o Recognises & binds wade variety of bacteria & fungi
o Acts as an opsonin ie ↑phagocytosis & complements action
Cellular
Factors
of
Innate
System
Natural Killer Cells
• =10-15% blood lymphocytes
• non thymic
• aka large granular lymphoctytes
• don’t have TLRs (no antigenic surface markers of T/B cells)
• part of innate immune system – but are regulated by T cells ∴ also role in adaptive immunity
• Different cytokines/interferons regulate NK cells – proliferate or kill
• role to kill with no presensitisation:
o tumour cells
o virally infected cells
o some normal cells
• activity mediated by balance of activating & inhibitory receptors:
o inhibition by recognition of self class I MHC molecules
! = killer inhibitory receptors
• all nucleated normal cells express class I MHC
! virally infected cells ↓s expression of class I MHC ⇒ NK cell lysis (in conjunction with
activating receptors
• NKs also secrete cytokines:
o IFN-y ⇒
! activate macrophague
! differentiate CD4+ cells ⇒ TH1 cells
o TNF
o Granulocyte macrophague colong stim factor (GM-CSF)
Neutrophils
• 80-90% of circulating polymorphs
• contain: lysozymes, phagosomes, ingested organisms, phagolysozomes
• are able to penetrate endothelial surface under influence of chemotactic factors
Esinophils
• can phagocytose
• can degranulate adjacent large foreign bodies (which too large for phagocytosis) eg worms
• attracted by eosinophil chemotactic factor
• attach to Ig’s & foreign particles
• release:
o major basic protein
o eosinophil cationic protein
o anti-inflam enzymes
• may have role in immune down regulation
Basophils & Mast Cells
• limited no in circulation
• predominantly assoc with epithelial cells esp mast cells
• may play role in immunity to parasitic infections ie ↑ed response
Phagocytes
• Phagocytes recruited to site of infection ⇒ inflam
• Phagocytes recognise microbes by receptors for:
o mannose residues not produced by host
cells
Immunology - 3
