31. Introduction to the Immune System and the threats to the body Flashcards
pathogenic microbes:
*Bacteria
*Viruses
*Fungi
*Parasites
Immune responses can be made to non-infectious substances:
Environmental molecules (allergy)
Tumours
Host components (autoimmunity)
Involved in tissue homeostasis and repair
Immunology:
Study of immune responses and
associated cellular and molecular events
2 types of IMMUNITY
- INNATE IMMUNITY (natural/native)
- ADAPTIVE IMMUNITY (acquired/specific)
Cooperation between the both types of immunity
what is INNATE IMMUNITY and how is its response?
(natural/native)
- FIRST LINE of host defence against infection
- Always present in health
- Provides IMMEDIATE protection - RAPID RESPONSE
what is ADAPTIVE IMMUNITY and how is its response?
(acquired/specific)
- Adapts more SLOWLY
- Specialised defence
- Proliferation and differentiation of lymphocytes
INNATE vs ADAPTIVE
I - CONSTITUTIVE (always on)
A - requires PRIMING by antigens
INNATE vs ADAPTIVE
response time?
I - RAPID response (minutes-hours)
A - SLOW response (days-weeks)
INNATE vs ADAPTIVE
specificity?
I - NON-SPECIFIC
recognises MOLECULAR PATTERNS (features common to a large
range of different microbes
A - SPECIFIC (recognises unique antigens)
INNATE vs ADAPTIVE
memory response?
I - NO memory response
A - MEMORY RESPONSE
INNATE vs ADAPTIVE
becomes more effective?
I - does NOT get more effective upon second exposure
A - becomes MORE EFFECTIVE with REPEATED EXPOSURES
what is an ANTIGEN
Molecules recognized by the immune system
- stimulating an immune response
what is an EPITOPE
PART of the ANTIGEN RECOGNISED and BOUND by ANTIODY or by ANTIGEN RECEPTORS on T and B CELLS (of ADAPTIVE immune system)
an antigen can have several different epitopes or repeat epitopes
CELLS of INNATE IMMUNE SYSTEM: (3)
- SENTINELS
- PHAGOCYTES
- INNATE LYMPHOID CELLS
SENTINELS
(e.g. mast cells, dendritic cells,
macrophages)
- TISSUE resident
- RECOGNISE invading pathogens
- ALERT immune system
secrete inflammatory mediators
PHAGOCYTES
(e.g. neutrophils, macrophages,
dendritic cells)
- TISSUE resident or recruited from BLOOD
- ENGULF and KILL invading pathogens
- ALERT ADAPTIVE immune system (DCs, macrophages) (through release of inflammatory mediators)
INNATE LYMPHOID CELLS
(e.g. NK cells, ILC)
- TISSUE resident or recruited from BLOOD
- KILL INFECTED or TRANSFORMED cells (NK cells)
- produce CYTOKINES
what are CYTOKINES
family of SMALL PROTEINS
- used for COMMUNICATION in the
immune system.
(soluble mediators in both INNATE and ADAPTIVE)
Cells are stimulated to produce cytokines which are recognised by other cells which respond to the cytokine
Cytokines play diverse roles in the REGULATION of an immune response:
LOCATION
MAGNITUDE
TYPE
what are ACUTE PHASE PROTEINS
SOLUBLE MEDIATORS in INNATE immune system
-synthesised in LIVER
- proteins whose SERUM CONCENTRATIONS INCREASE during INFLAMMATORY RESPONSE
what are COMPLEMENT cells
SOLUBLE MEDIATORS in INNATE immune system
(can be considered to be part of acute phase proteins family)
- can RECRUIT more cells to the area of infection
- can COAT PATHOGENS so they are ingested and destroyed by phagocytes more READILY
- involved in the CLUMPING together and LYSIS of target cells
how do SENTINAL CELLS RECOGNISE infection
by PATTERN-RECOGNITION RECEPTORS (PRRs) on sentinel cells
what do PATTERN-RECOGNITION RECEPTORS on SENTINEL CELLS recognise: (2)
- PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs)
common to groups of bacteria, fungi
or viruses but are not commonly found on host cells - DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPs/ alarmins) (or danger-associated)
Molecules released from dying cells or damaged connective tissue.
both are molecules not normally seen by a healthy cell or normal situation
7 steps of INNATE immune response
- injury, barrier break, MICROBE ENTRY
- microbes/injury ACTIVATE SENTINEL CELLS (recognition by PRRs)
- sentinel cells secrete INFLAMMATORY MEDIATORS (inflammatory response)
- VASODILATION and increasing VASCULAR PERMEABILITY - FLUID and PROTEINS ENTER TISSUES
- complement, antibodies & antimicrobial proteins KILL MICROBES
- RECRUITMENT. adhesion molecules and chemokines cause LEUKOCYTE MIGRATION into tissue
- PHAGOCYTOSIS and KILLING of microbes
what are the 5 CARDINAL SIGNS of INFLAMMATION
HEAT (Calor)
REDNESS (Rubor)
SWELLING (Tumor)
PAIN (Dolor)
LOSS OF FUNCTION (Functiolaesa)
what is PHAGOCYTOSIS
the ENGLULDING of microorganisms or other cells and foreign particles by PHAGOCYTES
(e.g. sentinel macrophages and recruited neutrophils)
- engulfs to form PHAGOSOME
- fuses with lysosome to form PHAGOLYSOSOME
(enzymes to hydrolyse)
how do INNATE immune cells ALERT ADAPTIVE immune system (3 steps)
using ANTIGEN PRESENTING CELLS eg. dendritic cells
- APC eg dendritic cells RECOGNISE, INGEST and DEGRADE PATHOGEN
- pieces of pathogen - PEPTIDE ANTIGENS- are DISPLAYED on the CELL SURFACE
- moves around body to find cell that recognises antigen and
ENTERS LYMPHATIC VESSEL
TRAVELS to LYMPH NODE
to encounter LYMPHOCYTE that can recognise the presented antigen
what happens when a DENDRITIC CELL presenting the PEPTIDE ANTIGEN enters a LYMPH NODE
- PRESENT PEPTIDE ANTIGENS to T CELLS
- SMALL number of T CELLS RECOGNISE the peptide antigen
- T CELLS become ACTIVATED and PROLIFERATE
CD8+ cytotoxic, CD4+ helper - CD4+ HELPER T CELLS support B CELL ACTIVATION and production of ANTIBODIES
what do HELPER T CELLS (CD4+) do
release CYTOKINES and ACTIVATE other cells of the immune system
HELP B CELLS to produce ANTIBODIES and promote MACROPHAGE KILLING
e.g. macrophage killing of phagocytosed or intracellular pathogens.
(Regulatory T cells SUPRESS the activity
of other immune cells)
what do CYTOTOXIC T CELLS (CD8+) do
KILL INFECTED CELLS with intracellular pathogens eg. viruses
and release CYTOKINES
what do B CELLS do
produce ANTIBODIES
what do ANTIBODIES from B cells do
BIND to and NEUTRALISE PATHOGENS,
enhance PHAGOCYTOSIS of pathogens,
ACTIVATE the COMPLEMENT CASCADE
T CELLS and ANTIBODIES return to…
the site of infection to eliminate pathogens or infected cells
3 ADAPTIVE immune cells
- CD4+ T CELLS (HELPER)
- CD8+ T CELLS (CYTOTOXIC)
- B CELLS
where are T CELLS DEVELOPED
THYMUS
where are B CELLS DEVELOPED
BONE MARROW
ANTIBODIES (immunoglobulins) are comprised of:
2 HEAVY CHAINS
2 LIGHT CHAINS
2 IDENTICAL ANTIGEN BINDING SITS (variable region - specific)
what does the N-TERMINUS of each HEAVY CHAIN do to form the FAB REGION of an antibody
N-TERMINUS of each HEAVY CHAIN`
ASSOCIATES with ONE of the LIGHT CHAINS to create 2 ANTIGEN-BINDING DOMAINS (Fab region)
how is Fc REGION of an antibody formed
C-TERMINUS of the 2 HEAVY CHAINS COMBINE to form Fc region
Fc region of the antibody can be involved in:
- COMPLEMENT ACTIVATION
- INTERACTION with other immune cells via Fc RECEPTOR BINDING
- production of DIFFERENT ANTIBODIES: IgG, IgE, IgD, IgA, IgM
which have different functions
type of antibodies involved in BLOCKING & NEUTRALISATION
IgG, IgM, IgA
types of antibodies involved in: COMPLEMENT FIXATION
IgM, IgG
types of antibodies involved in:
OPSONISATION and KILLING
IgG & IgE
types of antibodies involved in:
MAST CELL ACTIVATION
IgE
B CELLS RECOGNISE ANTIGENS through…
B-CELL RECEPTORS (BCRs)
which B-cells are the first to appear
those carrying IgM markers
ANTIBODIES are SECRETED VERSIONS of..
B-CELL RECEPTOR
- and have same ANTIGEN SPECIFICITY
where are ANTIBODIES FOUND
in SERUM and other BODILY FLUIDS
What can ANTIBODIES ACTIVATE to kill pathogens
COMPLEMENT
BINDING and NEUTRALISATION occurs through which region of the ANTIBODY
FAB REGION
ENHANCED UPTAKE BY PHAGOCYTES and COMPLEMENT ACTIVATION occurs by which region of the ANTIBODY
Fc REGION
T-CELLS RECOGNISE specific ANTIGENS through…
T-CELL RECEPTORS (TCRs)
do T-CELLS and B-CELLS recognise antigens in the same way?
NO
recognise in DIFFERENT ways
how do B-CELLS RECOGNISE ANTIGENS (with BCRs)
recognise antigens CIRCULATING FREELY, or ATTACHED to the SURFACE of MICROBES.
These are often large molecules
- B cells recognise only a
SMALL portion or “EPITOPE” on the
external surface of the molecule.
how do T-CELLS RECOGNISE ANTIGENS (with TCRs)
CANNOT directly recognise
free antigen.
T cell antigen receptors recognise PEPTIDES PRESENTED to them by
MAJOR HISTOCOMPATIBILITY COMPLEX
(MHC) MOLECULES.
An ACCESSORY CELL is required to PROCESS and PRESENT the ANTIGEN to T cells
eg dendritic cells
what are MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) MOLECULES
- cell surface molecules
- main function is to PRESENT ANTIGENS to T CELLS
human MHC is known as HUMAN LEUKOCYTE ANTIGEN (HLA) COMPLEX
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) MOLECULES are HIGHLY…
HIGHLY POLYMORPHIC
owing to selective pressures on immune system to recognise highly VARIABLE and constantly MUTATING PATHOGENS
- MOST POLYMORPHIC GENES in human genome
2 types of MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) MOLECULES:
- CLASS I MHC
- CLASS II MHC
CLASS I MHC
are expressed on… and recognised by…
- EXPRESSED on ALL NUCLEATED CELLS
- RECOGNISED by CD8+ CYTOTOXIC T-cells
CLASS II MHC
are expressed on… and recognised by…
- EXPRESSED on ANTIGEN PRESENTING CELLS
- RECOGNISED by CD4+ HELPER T-cells
Lymphocytes go from Generative Lymphoid Organs (thymus/bone marrow) to circulation to SECONDARY LYMPHOID ORGANS eg…
LYMPH NODES
SPLEEN
MUCOSAL and CUTANEOUS LYMPHOID TISSUES
- where lymphocytes encounter antigens
Immature T lymphocytes MIGRATE from BONE MARROW to THYMUS where..
each CLONE GENERATES a UNIQUE T-CELL ANTIGEN RECEPTOR
what happens in THYMUS to PREVENT AUTOIMMUNE DISEASE
DELETION
many T-CELLS recognise SELF ANTIGENS and DELETE
(some escape –regulatory T cells)
Naïve T cells which ESCAPE DELETION..
- have POTENTIALLY USEFUL RECEPTORS AGAINST FOREIGN ANTIGENS
-exported from thymus and CIRCULATE around body
Most activated T and B cells become short-lived effector cells.
Some activated T-CELLS and B-CELLS cells become…
LONG-LIVED MEMORY CELLS
how is the SECONDARY RESPONSE (second exposure to pathogen) when there are MEMORY cells (T or B)
- FASTER
- LARGER (more antibodies produced)
IgG dominate (primary response: IgM)
examples of FAILURE of the Immune System (3)
- ALLERGY : unwanted response to harmless antigens
- AUTOIMMUNITY: response to body’s own antigens
(also, chronic inflammation driven by inappropriate responses to commensal flora) - IMMUNODEFICIENCY: failure to respond to pathogens owing to primary (after birth) or secondary (later in life) defect in
the immune system.
Pathogens are first recognised by
INNATE Immune System
- comprising soluble and cellular components
activate ADAPTIVE immune system
ADAPTIVE immune system generates
IMMUNOLOGICAL MEMORY