immunology
WHAT IS THE IMMUNE SYSTEM?
Definition
The immune system is:
a system of cells, tissues and soluble molecules
that recognises, attacks and destroys foreign entities
Purpose:
protection
homeostasis
survival
HOMEOSTASIS
Definition
Maintaining internal stability despite changing conditions.
Important:
dynamic process
not fixed/static
The immune system constantly adjusts to maintain balance.
THREE MAIN IMMUNE SYSTEM COMPONENTS
1. Recognition system
Detects invaders.
2. Disposal system
Kills/eliminates threats.
3. Communication system
Coordinates immune response.
Uses:
cytokines
chemokines
“SELF” VS “NON-SELF”
Important concept:
Humans contain huge numbers of microbes:
microbiome
virome
So “foreign” is complex.
MICROBIOME
Definition
Microorganisms living in/on the body.
Important:
many are beneficial
help metabolism and protection
Humans can be considered:
superorganisms
PATHOGENS VS PATHOBIONTS
Pathogens
Microorganisms causing disease.
Example:
viruses
bacteria
Pathobionts
Normally harmless microbiome organisms that can become pathogenic.
TYPES OF PATHOGENS
Extracellular pathogens
Remain outside host cells.
Examples:
many bacteria
Intracellular pathogens
Enter host cells to replicate.
Examples:
viruses
OBLIGATE VS FACULTATIVE INTRACELLULAR PATHOGENS
Obligate
Must live inside cells.
Example:
viruses
Facultative
Can live:
inside OR outside cells
Example:
some bacteria
IMMUNOPATHOLOGY
Symptoms of infection often result from:
immune response itself
NOT only pathogen damage.
THREE PHASES OF IMMUNE RESPONSE
Phase 1
Immediate innate defence.
Includes:
skin barrier
mucosa
enzymes
Phase 2
Pathogen-induced innate response.
Includes:
inflammation
complement
phagocytosis
Phase 3
Adaptive immune response.
Includes:
B cells
T cells
antibodies
INNATE VS ADAPTIVE IMMUNITY
Innate | Adaptive |
Rapid | Slower |
Broad recognition | Highly specific |
No memory | Has memory |
Phagocytes important | Lymphocytes important |
CELLS OF THE IMMUNE SYSTEM
All arise from:
hematopoietic stem cells in bone marrow
MYELOID CELLS
Include:
neutrophils
macrophages
eosinophils
basophils
monocytes
Mainly:
innate immunity
LYMPHOID CELLS
Include:
B cells
T cells
NK cells
Mainly:
adaptive immunity
GRANULOCYTES
Leukocytes containing:
intracellular granules
Granules contain:
microbe-killing molecules
INNATE IMMUNITY — PATHOGEN RECOGNITION
MOST IMPORTANT CONCEPT
Innate immunity recognises:
PAMPs
(Pathogen-Associated Molecular Patterns)
Examples:
bacterial LPS
PRRs
Host receptors recognising PAMPs.
Called:
PRRs
(Pattern Recognition Receptors)
IMPORTANT EXAMPLE
TLR4
A Toll-like receptor recognising:
LPS from Gram-negative bacteria
WHAT HAPPENS AFTER PATHOGEN RECOGNITION?
Three major responses:
Complement activation
Inflammation
Phagocytosis/internalisation
COMPLEMENT SYSTEM
Definition
Group of ~30 serum proteins.
Functions:
pathogen lysis
opsonisation
inflammation
OPSONISATION
Definition
Coating pathogens to improve phagocytosis.
Makes pathogens easier for immune cells to engulf.
INFLAMMATION
Purpose
Recruit and activate immune cells.
MAIN FEATURES
Vasodilation
↑ blood flow.
Chemokines
Guide immune cells to infection site.
Cytokines
Activate immune cells.
CLASSIC SIGNS
redness
swelling
fever
PHAGOCYTOSIS
Performed by:
macrophages
neutrophils
dendritic cells
Steps:
engulf pathogen
digest pathogen
destroy pathogen
DENDRITIC CELLS
VERY IMPORTANT.
Function:
antigen presentation
link innate → adaptive immunity
ADAPTIVE IMMUNITY
Main cells
B lymphocytes
Produce antibodies.
Cytotoxic T cells (Tc)
Kill infected cells.
Helper T cells (Th)
Activate other immune cells using cytokines.
PRIMARY VS SECONDARY LYMPHOID ORGANS
Primary lymphoid organs
Where lymphocytes mature.
Bone marrow
B cell maturation
Thymus
T cell maturation
Secondary lymphoid organs
Where lymphocytes:
encounter antigen
become activated
Examples:
lymph nodes
spleen
GENERAL FEATURES OF ADAPTIVE IMMUNITY
Specificity
Specialisation
Memory
Diversity
Tolerance
SPECIFICITY
Adaptive immunity recognises:
specific antigens
NOT general PAMPs.
ANTIGENS
Definition
Molecules recognised by lymphocytes.
Antigen = antibody generation.
BCR & TCR
BCR
B-cell receptor.
TCR
T-cell receptor.
SPECIALISATION
B CELLS
Produce antibodies.
Best against:
extracellular pathogens
CYTOTOXIC T CELLS
Kill infected cells.
Best against:
intracellular pathogens
HELPER T CELLS
Activate:
B cells
Tc cells
macrophages
Using:
cytokines
ANTIGEN PRESENTATION
KEY EXAM CONCEPT
T cells do NOT recognise pathogens directly.
Antigens must be presented by:
antigen-presenting cells (especially dendritic cells)
MHC
Major Histocompatibility Complex.
Displays antigen peptides on cell surface.
MHC CLASS II
Used for:
extracellular pathogens
Presented to:
helper T cells
MHC CLASS I
Used for:
intracellular pathogens
Presented to:
cytotoxic T cells
IMMUNOLOGICAL MEMORY
Adaptive immune system remembers pathogens.
After first exposure:
memory B cells
memory T cells formed
Second exposure:
faster
stronger response
PRIMARY VS SECONDARY RESPONSE
Primary response
Slow initial response.
Secondary response
Faster and stronger due to memory cells.
ANTIBODY DIVERSITY
Huge number of antibodies possible:
≈ 10¹¹
HOW DIVERSITY IS GENERATED
Main mechanism:
V(D)J\ recombination
Other mechanisms:
junctional diversity
heavy/light chain pairing
somatic hypermutation
TOLERANCE
Definition
Mechanisms preventing immune attack against self.
CENTRAL TOLERANCE
Occurs during:
early lymphocyte development
PERIPHERAL TOLERANCE
Occurs after lymphocytes enter circulation/tissues.
MOST IMPORTANT EXAM CONTENT
Prioritise:
innate vs adaptive immunity
PAMPs vs PRRs
complement system
inflammation
phagocytosis
B cells vs T cells
MHC I vs MHC II
antigen presentation
immunological memory
antibody diversity
tolerance
BIG PICTURE OF THE WHOLE LECTURE
Pathogen enters body →
innate immunity recognises PAMPs via PRRs →
inflammation/complement/phagocytosis activated →
dendritic cells present antigens →
adaptive immunity activated →
B cells make antibodies →
Tc cells kill infected cells →
memory cells formed →
faster secondary response in future.