Human immune system Flashcards
(23 cards)
B cell maturation
Occurs in the bone marrow
B lymphocytes bind to self-antigens and undergo apoptosis
Naive B cells meet antigens in secondary lymph organs
They’re activated when their surface receptors bind to a specific epitope on an antigen
CD4+ T helper cells produce cytokines to drive differentiation
What does the activation of B cells result in
Activation results in clonal expansion and differentiation into plasma and memory cells
Plasma cells produce soluble antibodies against the same epitope
Memory cells remain in circulation but don’t produce antibodies
Antibody structure
Immunoglobin consists of two identical short polypeptides (light chains) and two identical longer polypeptides (heavy chains)
The four chains are held by disulfide bonds
Fab regions - the two arms
Fc region - the stem
Properties of immunoglobin chains
Each Ig chain has a variable region;
The amino acid sequence differs
Antigen-binding site
Forms antigen-antibody complexes
The constant region;
5 heavy chain constant regions
5 classes - IgM, IgD, IgG, IgA, IgE
What is humoral immunity
B cell lymphocytes generate antibodies
Diversity between antibodies is created through DNA rearrangement
An Ig protein is encoded by different segments of DNA (somatic recombination)
V (variable), D (diversity), J (joining) where V, D and J are chosen by any cell and appears to be random
The primary immune response
Only a few B or T cells recognise the antigen and mount a response
Clonal expansion
Memory cells
Isotype switching (IgM –> IgG, IgA or IgE)
The secondary immune response
A large clone of memory cells can recognise the antigen
The immune response is faster and more effective
Vaccination works through the primary and secondary response
Antibodies can cause hypersensitivity (allergy) and auto-immune responses
Hypersensitivity caused by mast cells
An immune cell that lives in the skin and produces histamine
The activation of T and B cells with receptors that recognise antigens on an allergen
An allergen activates the immune system but isn’t necessarily harmful
Differentiation of plasma cells produce IgE antibodies specific to the allergen
Fc portion of IgE irreversibly binds to Fce receptors on mast cells
Mast cells are now ready to respond to the antigen the next time it’s encountered
Allergen binds to IgE receptors on mast cells
It will rapidly release histamine, proteases and other inflammatory molecules
Severe allergic reactions cause anaphylaxis. Symptoms include…
Feeling faint
Loss of consciousness
Breathing difficulties
Fast heartbeat
Swelling of face and lips
Can be reversed by adrenaline which relaxes the airway and reduces swelling in the throat
Maintains heart function and blood pressure
Prevents further release of histamine
Auto-immunity
Caused by a failure of immune tolerance
Recognition of one’s own cells and tissues as foreign
Production of auto-reactive T cells and auto-antibodies by B cells
Causes inflammation and organ damage
Type 1 diabetes and thee immune response
Caused by the destruction of beta cells
Auto-reactive T helper cells activate auto-reactive B cells which produce auto-antiboides
Auto-reactive cytotoxic T cells recognise self-peptides and kill beta cells
Results in hyper-glycaemia as glucose can’t enter cells where it’s needed
Symptoms of Type 1 diabetes
Increased thirst
Frequent urination
Increased hunger
Weight loss
Blurred vision
Fatigue
UTIs
Long-term dysregulation of blood glucose can cause damage to the kidneys, eyes and blood vessels
Treatment of Type 1 diabetes
Injection of insulin with or after food
Risk of hypoglycaemia if too much insulin is injected
Can be reversed by sugary drinks or food with a high glucose content
HIV
A direct attack on T helper lymphocytes
Binds to CD4 proteins and is endocytosed
CD4 T helper cells die or are killed by cytotoxic T lymphocytes
An individual is considered to have AIDS when their T helper cell level drops significantly
This immunosuppression results in an increase in opportunistic infections and cancers
Influenza A
Wild aquatic birds are natural hosts and can transfer to other species
Highly virulent causing severe disease and pandemics
Sub-divided into different serotypes based on antibody response
13 distinct H subtypes and 9 N subtypes based on two surface proteins
Hemagglutinin (viral entry)
Neuraminidase (viral exit)
Examples include H5N1 avian strain in Asia (bird flu) or H1N1 strain in Mexico 2009 (swine flu)
H5N1 - low transmission rates, deep in lung
H1N1 linkage - easily transmitted, expressed in epithelial cells in the upper respiratory tract
Influenza B
Almost exclusively infects humans (also seals and ferrets)
Less common than A
Mutates 2-3 times slower than A
Immunity in humans is acquired at an early ages
Limited host range and slow mutation rates so no pandemic and cross-species infections
Influenza C
Infects humans, dogs and pigs
Less common than A and B
Mild disease in children
Cause cause severe illness and localised pandemics
Influenza virology
Roughly spherical
Viral envelope, two major glycoproteins
Central core proteins contain RNA genome and other proteins that package and protect RNA
RNAs are negative strands that must be copied to a positive strand for translation
Hemagglutinin (HA)
A lectin that mediates binding and entry of viral genome into the target cell
It binds via sialic acid on the surface of epithelial cells
Neuraminidase (NA)
Involved in the release of viral progeny from infected cells by cleaving sugars that bind mature viral particles
Ion channel M2 promotes an influx of H+ ions into endocytic vesicles during viral infection of target cells
Antigenic drift
Mutations are frequent because viral RNA polymerase has no proof-reading ability
Results in slight changes in amino acid structure of surface proteins (HA and NA)
Changes result in decreased affinity or inability of antibodies/T cells to bind effectively
Trivalent influenza vaccine (TIV)
Purified and inactivated antigens from 3 viral strains, usually two A subtypes and one B
Vaccine is formulated for one year as the virus evolves rapidly
Activation of the adaptive immune response
Receptors on B and T lymphocytes recognise surface proteins of the virus (HA or NA)
These can block virus entry or kill infected cells
If viral antigens are altered then new lymphocyte clones must be activated
This takes time during which the virus replicates and infects more cells which can cause breathing difficulties and fever
Fatigue develops via a cytokine storm
