6: Immune Response to Infection Flashcards
6 receptors for immune response
MHCI
MHCII
TCR
BCR
B7
CD40
MHCI receptor
on all nucleated cells
endogenous peptides = face of the cell, tell immune cell they are own cell
MHCII receptor
on all antigen presenting cells(DC, macrophages and B cells),
have exogenous peptides
TCR receptor
T-cell receptor
antigen-specific
self-reactive potential
BCR receptor
B cell receptor
IgM cell surface receptor
antigen-specific
self-reactive potential
B7 receptor
on antigen presenting cells
co-stimulation CD28
T cell activation
CD40 receptor
B cell receptor
co-stimulation CD40L
B cell activation
Roles of complement system
Anaphylatoxins
Chemokines
Opsonisation
Membrane Attack Complex
Lectins
neutralise and opsonise pathogens
What cells have complement receptors
innate immune cells
Interferons are
cytokines produced by both immune and infected cells in response to viruses and Gram -ve bacteria
produce antiviral proteins in response
Type I and III interferons promote
antiviral response
Type II interferons promote
antibacterial response
Opsonisation
Antibodies, complement factors and lectins bind to pathogenic surface
Recognised by innate immune cells
aid phagocytosis
neutralise pathogenic cell surface
activation of complement cascade (classical pathway)
What is the difference between MHCI and MHCII
MHCI shows peptides from inside the cell (endogenous)
MHCII shows peptides from outside the cell (extrinsic)
Detection of tissue damage
damage associated molecular patterns DAMPS initiated
Detection of pathogenic structures
pathogen associated molecular pattern PAMPs initiated
Activation of innate immune system is a
non-specific response
DAMPS and PAMPS cause
activation of innate immune system
attack pathogens and liaise with adaptive immune cells
cause non-immune cells to produce anti-microbial peptides (interferons)
Innate immune system
pre-determined, present at birth
Pattern recognition receptors - same cell types recognise same pathogens using same receptors
Receptors involved in innate immune system
TLRs, Fc receptors, complement receptors, scavenger receptors
What kind of immunity does the liver produce
innate humoral immunity:
-lectins - neutralise and opsonise
-complement factors -opsonisation, chemotaxis, MAC
Cellular innate immune cells
Granulocytes : neutrophils, basophils, eosinophils, mast cells, monocytes, macrophages
natural killer cells
dendritic cells
First responders in immune response
Neutrophils - short lived ~6h
Naive/inactive cells become activated by
pathogens
start secreting cytokines and chemokines
Where do macrophages reside
Tissues or circulationMs
Macrophage activation
expresses new genes for infection
Do NKC have MHCI
no
How can Viruses and cancer cells evade detection
by MHCI downregulation
NK cells, kill :
nucleated cells without MHCI
opsonised cells or pathogens via antibodies and complement
Adaptive immune system
takes time
correct specific cell found
2 receptors: TCR and IgM receptors (BCR)
all lymphocytes have different receptors
Clonal lineage in infection has same receptor
Memory cells with same receptors enable quick immunity if reinfected
2 receptors of adaptive immune system
TCR
IgM receptors (BCR)
Humoral response of antibodies is produced by
B plasma cells
Initiation of adaptive immune system
Activated macrophages and DCs present antigens in combination with MHCI or MHCII to T-cells
- cytokines produced by antigen presenting cells; activate T cells
-T cells provide cytokines that activate and stimulate phagocytes
T-cells are activated by
MHC and foreign peptide recognition from APC
T cells interact with B cells to
activate specific B cells to produce antibodies
- B cells licensed for antibody production
Four functions of T cells
Activate phagocytes
Activate B cells
Directly kill infected cells
Regulate immune response
Two functions of B cells
Present soluble antigen to T-cells
produce antibodies
Sequence of immune response
- Innate immune cells recognise pathogen and become activated
- Start secreting cytokines and phagocytose pathogens
- Antigen presenting cells move to lymph nodes to find specific lymphocytes
- T helper cells proliferate and differentiate into specific type
- Cytotoxic CD8+ T cells attack pathogens directly, B cells become activated
- Activated B cells differentiate into plasma B cells and start antibody production
- Phagocytes and complement cascade attack antibody-opsonised cell
- Response of antibody production peaks 2 weeks after infection
After pathogen clearance
immune cells undergo apoptosis
supressed production of inflammatory cytokines
cell population contracts, some form memory cells
tissue repair and remodelling
Inflammatory diseases are
Positive feedback loops
Effect of damage to tissues on immune response
stronger immune response
Immunity occurs due to 2 mechanisms
1.Formation of memory B and T cells
2. In re-exposure, antibody response is greater, more plasma cells keep producing protective serum antibodies
both involved during vaccination
Memory cells in lymphoid tissues are in
lymph nodes
spleen
gastrointestinal mucosa (e.g Peyer’s patches)
Mucosal epithelia
Bone marrow
Memory cells in circulation
Memory T cells - constantly migrate from and to lymphoid tissues
Memory B cells can differentiate into plasma cells, secreting antibodies
Memory cells after immune response
do not contract
Thymic involution
Thymus shrinks in size
stops producing new naive T cells
over time, more T cells become activated and change from naive T cells to memory cells, so no. naive cells goes down and memory T cell no. goes up
A 1 year old is exposed to Staphylococcus aureus by a cut to his finger, what is the order of immune cell activation in response to this infection
Neutrophil > macrophage > DC > T cell > B cell
-neutrophils are first to encounter pathogen in tissues
-macrophages first to encounter pathogen in blood
-macrophages then signal dendritic cells which activate Th cells via MHC II antigen presentation
-T-helper cells migrate to lymphoid tissues and activate B cells with complementary receptor to pathogen
A baby is born with Severe Combined Immunodeficiency SCID but doesn’t develop an illness from a virus, what could explain this?
Child has IgG antibodies against the virus
- obtained from mother via placenta, providing acquired immunity
What does immunoglobulin gene arrangement allow for
large variety of B cell receptors in body, without need for equally large gene repertoire
during reshuffling process, VDJ or VJ recombinase enzyme used to cut any unneeded genes, leaving new gene sequence that can produce a randomly unique B cell
SCID (severe combined immunodeficiency)
caused by : deficiency in Rag1 and Rag2 - essential proteins in VDJ or VJ recombinase
immune system deficiency as patient can barely do immunoglobulin gene rearrangement, so don’t have wide range of B cells
What is seen to be elevated in a blood sample soon (2 days) after initial infection
Mannose-binding lectin ; acute phase protein found in incr. conc. in blood in the first few days of infection
Acute-phase responses happen alongside
inflammatory response
- happen to continue to fight infection
- aim to produce more components (acute phase proteins) to continue fighting infection
Examples of acute-phase proteins
C reactive protein
mannose-binding lectin
fibrinogen
complement proteins
Mannose-binding lectin
acts as an opsonin of innate immune system by activating lectin pathway of complement system to aid fight against infection
Allows foreign substances to be efficiently identified for phagocytosis
In the case of immunosupression, how can an immune response still be carried out
Complement system can fight infection
- alternate pathway of complement system which doesn’t require antibodies or mannose binding lectin
- triggered by surface-activation via presence of bacterial endotoxins
