ICS - Immunology Flashcards
What do toll like receptors respond to?
PAMPs - Pathogen
DAMPs - Damage
Associated Molecular Patterns
Important TLRs (apparently)
2,4,5,7,9
2- G+ and TB (extracellular)
4 - lipopolysaccharides (G-) (extracellular)
5 - Flagellin (extracellular)
7 - Single strand RNA (intracellular)
9 - unmethylated CPG DNA (intracellular)
Which TLRs are intracellular
3,7,8,9
All TLRs (1-11) and what they recognise
*2 - gram positive + TB
3 - viral dsRNA
*4 - Lipopolysaccharides (G-)
*5 - Flagellin
6 - Lipoteichoic acid (G+)
*7 - single stranded RNA
8 - DSRNA (G+)
*9 - CPG (non methylated) DNA (bacteria)
11 - bacteria (urogenital pathogens)
1,2,6 - bacterial cell wall components
3 - dsRNA
4 - G- LPS
5 - flagellin
7 - ssRNA
9 - unmethylated CpG
Innate vs adaptive immunity
Innate
- Non specific
- Resistance not improved by reinfection
- Instinctive
- Rapid response
- Phagocytes and natural killer cell
- No memory
Adaptive
- Specific “acquired” immunity
- Resistance improved by repeat infection
- Slower response
- Requires lymphocytes (T&B)
- Memory
Clinical indications of an allergic reaction
(Skin, Airways, GI)
Skin - Swelling, itching, reddening
Airways - Excessive mucus production, bronchoconstriction
GI - Abdominal bloating, vomiting, diarrhoea
What stem cell do blood cells originate from
Haematopoietic pluripotent stem cell
What are the 3 ways the complement system destroys pathogens
Innate immunity
- Direct lysis - (membrane attack complex) - Group of complements make a hole in pathogen
- Opsonisation - (C3b) antigen coated with complement that makes it easier to phagocytose
- Increase inflammation - (C3a and C5a)
Neutrophil properties
65% of blood
Lifespan: 6 hours - 12 days
Contain primary lysosomes and secondary granules which secrete toxic substances to kill microbes
Key role in innate immunity and inflammation
Monocyte properties
Lifespan: months
Innate (phagocytosis) and adaptive (antigen presentation) roles
Differentiate into macrophages in tissue
Macrophage properties
Lifespan: Months/years
Kupffer cells in liver, microglia in brain
innate (phagocytosis) and adaptive (antigen presenting) role
First line non self recognition
Macrophage properties
Lifespan: Months/years
Kupffer cells in liver, microglia in brain
innate (phagocytosis) and adaptive (antigen presenting) role
First line non self recognition
Eosinophil properties
Lifespan: 8-12 days
Contain major basic protein (MBP) toxin, which activates neutrophils and induces histamine release
Granules stain using eosin (red/pink)
Often seen in parasitic infection
Basophil properties
Lifespan: 2 days
Express high affinity IgE receptors, which cause degranulation and release of histamine.
Similar to mast cells (mast cells fixed, basophils circulate in blood)
Granules stain using haemotoxylin (blue/violet)
T lymphocyte (t cell) properties
Hours-years
Originate in bone marrow but mature in thymus
Recognise antigens displayed by antigen presenting cells, which they bind to with t cell receptors.
Produce cyotkines
Found in blood, lymph nodes, spleen
T helper 1&2 (CD4)
Cytotoxic T cell (CD8)
T reg
Natural killer cells
Express CD56
Recognise and kill virus infected cells and tumour cells by apoptosis
Primary vs secondary lymphoid organs
Primary - Bone marrow (immune cell origin, b cell maturation site), thymus (t cell maturation site)
Secondary - Lymph nodes, spleen (Removal site of RBC and antibody coated bacteria)
Physical and chemical barriers in innate immunity
Physical - skin, mucus, cilia
Chemical - Lysozyme in tears, stomach acid
What are antigen presenting cells and 2 functions?
E.g. dendritic cells
Present foreign antigens to T helper cells.
Stimulates Th proliferation
or B cell production
Explain TLR 4
TLR activated by LPS on gram negative bacteria (endotoxin)
Trigger immune response (activate complement, cytokine release (TNFa, IL1,6), phagocytosis)
Explain Thymic tolerance
Thymic tolerance/selection used to see if immature T cells are functional. Any failed selection results in apoptosis.
+ selection (self recognition) - CD8 (Tc) binds to MHC-I, CD4 (Th) binds to MHC-II with moderate strength; recognise self. Allowed to survive.
- selection - If TCR (T cell receptor) on t cell recognises and binds to MHC-I or II (producing immune response to self) it has to be phagocytosed. TCR shouldnt interact with self
allocation - If immature T cell interacts with MHC-1: CD8 upregulated and becomes Tc cell
If reacts with MHC-2: CD4 upregulated, becomes Th cell
CD8 T cell function
Cytotoxic T cells interact with MHC-I
Direct killers - Secrete Perforin or express FAS to trigger apoptosis
CD4 T cell function
T Helper cells that interact with MHC-II
TH1 - IFNy - Activate NK cells and macrophages (innate immunity)
TH2 - IL4 - Activate B cells to differentiate into plasma cells (adaptive immunity)
Where are B cells produced and where do they mature
Both in bone marrow
Explain B cell activation
Th2 is activated by antigen presenting cell (dendritic cell) binding and MHC-II interactions.
It then releases IL 4 (causing B cell proliferation “clonal expansion”) and IL 5 (causing B cell differentiation into plasma cells which produce immunoglobulins)
Give a brief overview of IgG
Most abundant in blood
Key in secondary immune response (marker of immunological memory)
Give a brief overview of IgA
Most abundant in total body. Found on mucosal linings, in colostrum and in breast milk. Forms dimer
Give a brief overview of IgM
First Ig released in adaptive response
Forms pentamer
Give a brief overview of IgE
Found in type 1 hypersensitivity (anaphylaxis)
Activates mast cell/basophil degranulation
Give 3 functions of MHC molecules
Ensure T cells recognise self (positive selection)
Check T cells can confer immunity and dont cause autoimmunity (negative selection)
Confer autoimmunity to HLA (human leukocyte antigen) related inherited autoimmune conditions
Give the genes that cause these autoimmune conditions
Spondyloarthropathies
T1DM
Coeliac
SLE
All found on chromosome 6
Spondyloarthropathies: HLA-B27
T1DM: HLA-DR2DQ3
Coeliac: HLA- DQ2 (or DQ8)
SLE: HLA B8
Explain type 1 hypersensitivity with examples
IgE mediated (anaphylaxis)
IgE binds to mast cell/basophil causing degranulation and histamine release.
E.g. atopy (asthma, hay fever, rhinitis)
Explain type 2 hypersensitivity with examples
Antigen-antibody complex
IgG/IgM binds to antigen, activating MAC (complement) at SITE OF BINDING
E.g. Goodpastures, pernicious anaemia, rheumatic fever
Explain type 3 hypersensitivity with examples
Immune complex deposition at sites away from binding
IgG/IgA bind to antigen and activate complement at site of deposition
E.g. SLE, post strep glomerulonephritis, IgA glomerulonephritis
Explain type 4 hypersensitivity with examples
T cell mediated w/ delayed response
Th1 activated by APC, causing cytotoxic killing occurs around body
E.g. Type 1 diabetes mellitus, TB, MS, Guillain barre
Describe patient presentation of anaphylaxis
Severe hypotension
Tachycardia
Dyspnoea
Pale
Cold extremities
Puffed up face and tongue
Pruritus/itching
Central cyanosis
Explain treatment algorithm for anaphylaxis
1: ABCDE
Airway - can they breathe
Breathing - Rapid, wheezy, low SpO2? (<92%)
Circulation - pale, cold, clammy, low BP, capillary refill time?
Disability - Confused/comatose, movement
Exposure to antigen
2 - 500mcg IM adrenaline
Effects of histamine
Vasodilation, increased permeability (H1 receptor), bronchoconstriction facial flush, pruritus, swollen tongue/face
Describe immune tolerance
Non responsiveness to specific antigens to prevent self immune response
Central - occurs in the thymus/bone marrow during T/B cell maturation
Peripheral - Occurs after mature cells have been released into blood. Works to prevent autoimmunity, in secondary organs such as spleen.
Define autoimmunity
Pathological immune response against self either through faulty immune tolerance or molecular mimicry
Give examples of organ specific autoimmunity
T1DM - pancreas (b cells)
MS - Oligodendrocytes of CNS
Pernicious anaemia - parietal cells of stomach
Hashimoto’s - antibodies against TPO
Graves - Antibodies against TSH receptors
Give examples of non organ specific autoimmunity
SLE - affects DNA (ANA)
Autoimmune anaemia affects RBC
Autoimmune thrombocytic purpura affects platelets
Define immunodeficiency
The reduced ability of the body to fight infection or disease
Give some causes of immunodeficiency
Primary (Inherited): T/B cell defect/deficiency, IgA deficiency, CVID, SCID
Secondary (Acquired):
HIV, malnutrition, cancer, diabetes mellitus, chemotherapy, leukaemia, myeloma
Patterns of immunodeficiency
- Decreased CD4/T helper cells in HIV, leading to increased susceptibility to disease
- Deficient B cells (decreased plasma cells/antibodies)
- Neutrophil/macrophage deficiency (less phagocytosis/acute inflammation)
- Complement deficiency (innate immunity doesnt work as well)
- hyposplenism (lack of RBC recycling and killing of encapsulated bacteria)
Define active immunity with natural and artificial example
Active immunity involves:
Ig production, immunological memory and response largely secondary.
Natural: Body encounters pathogen, producing antibodies and memory cells
Artificial: Vaccine mimics encountering pathogen, stimulating Ig production
Define passive immunity, with natural and artificial example
Passive involves Ig’s passed directly to host with no memory and a primary response
Natural: maternal antibodies passed to feeding baby through breast milk/colostrum
Artificial: Antivenom, or Ig injection/transfusion
What are the aims of a perfect vaccine
- Achieve long term protection from small number of immunisations
- Stimulate BOTH B and T cells
- Induce memory B and T cells
- Stimulate protective IgG and IgA production
Active vs passive immunity
Active
- IgG production
- Immunological memory
- Secondary response
Passive
- IgG passed to host
- No memory
- Primary response
