Immunology Flashcards
What are the two primary lymph tissues
Thymus
Bone marrow
What’s the difference between primary lymph tissues and secondary lymph tissues
Primary = cells originate or mature Secondary = cells reside and traffic
what are the two cells that are only involved in adaptive immunity and not innate
B cells and T cells
what are the two cells involved in both innate and adaptive immunity
Natural killer T cell
yG T cell
what are the steps of phagocytosis
- Chemotaxis and adherence of microbe to phagocyte
2 ingestion of microbe by phagocyte
3 formation of a phagosome
4 fusion of the phagosome with a lysosome to form a phagolysosome
5 digestion of ingested microbe by enzymes
6 formation of residual body containing indigestible material
7 discharge of waste materials
what do activated macrophages secrete
cytokines and chemokines
which MHC classes do CD4 and CD8 interact with
CD4 = MHC class II
CD8 = MHC class I
What are the markers of a B cell
CD19 and CD20
What are the markers of Th cells
CD3 and CD4
What are the markers of Tc cells
CD3 and CD8
What is the marker on all T cells
CD3
what is the marker on NK cells
CD16/56
describe the signs of Specific IgA deficiency (sIgAD)
IgA protects against infections of the mucous membranes of the GI tract and airways
many asymptomatic
but sometimes associated with infections or autoimmune/allergic disease
next to no IgA
describe the signs of X linked agammaglobulinaemia (XLA)
Mutations in the BTK gene; X linked
• Causes arrest of B cell development between pro B to B cell stage
• No peripheral B cells in blood
• Failure of immunoglobulin production
describe type I hypersensitivity
IgE- mediated hypersensitivity
ALLERGEN induces a humeral response
- Secretes IgE antibody in response to activation of allergen-specific TH2 cells
- normally this happens when there’s a parasitic infection but if you have this then you have IgE regulatory defects (atopy) and that means there’s abnormal production of IgE in response to nonparasitic antigens
- Ag indices cross-linking of IgE (which is bound to mast cells, eosinophils and basophils) to allergen
- degranulation occurs
- leads to local or systemic inflammation
- IgE Abs bind with High Affinity to Fc eRI receptor on Mast Cells
Three Phases:
- Sensitisation phase:
• Exposure to allergen
- activates TH2 cells
- stimulate B cells to form IgE producing plasma cells
• IgE produced in response to antigenic stimulus and binds to FC- receptors on mast cells and basophils - Activation Phase:
•Re-exposure to antigen triggers mast cells and basophils to respond by release of their granules - Effector Phase:
• Complex response occurs as a result of histamine and other pharmacologically active agents released by mast cells and basophils
- can be systemic (anaphylactic shock) or localised (atopy)
- Allergic Reactions can have both an immediate phase but also a late-phase response
typically manifests as systemic and localised anaphylaxis such as hay fever, asthma, hives, food allergies and eczema
describe type II hypersensitivity
- Involves antibody-mediated destruction of cells
- cell destruction happens via Antibody-Dependent Cell mediated Cytotoxicity (ADCC)
- mediated by IgG and IgM
3 types: - blood transfusions - when incorrect blood type administered body has an immune response to the foreign blood - haemolytic disease of the newborn - drug- induced haemolytic anaemia (all of these cause haemolysis)
see hypersensitivity lecture for diagram on mode of action of ADCC
describe type III hypersensitivity
- immune complex-mediated hypersensitivity
- Reaction of Ab’s with antigen generates immune complexes
facilitating the clearance by phagocytic cells and mast cell activation - In some cases, large amounts of immune complexes can lead to
tissue damaging type III hypersensitivity reactions - Magnitude of the reactions depends on the amount of immune complexes
- Can be localized and occurs wherever immune complexes are deposited
- Common sites are blood vessel walls, synovial membrane of joints, glomerular basement membrane of the kidney
- Deposition of complexes results in the recruitment of neutrophils to the site (granular release)
- Lytic enzymes causes tissue damage
Examples:
- Farmer’s lung
- Pigeon fancier’s disease
- Serum Sickness (generalised) - when foreign antibodies are injected into human (eg from a mouse or something) - this is why in treatment we need to develop human antibodies treatment and not from animals
describe type IV hypersensitivity
Delayed-Type Hypersensitivity (DTH)
– Localized inflammatory response induced by T H
cells
– Characterized by large influx of inflammatory cells
and macrophages
– Delayed: 24-72 hours
– DTH is often helpful and plays important role in
intracellular pathogens and contact antigens
– DTH can cause tissue damage and be pathological if the pathogen and contact antigen persists - then DTH just keeps going and causes damage
Main examples:
- TB
- herpes
- measles
- contact antigens - jewellery, hair dyes etc
sensitisation and effector phase
- Influx and Activation of macrophages in the DTH response important in host defence against parasites and bacteria that live within cells
- ie. areas where Ab cannot reach them
- Normally the intracellular pathogen/infected cell is quickly cleared with little tissue damage, BUT if antigen not easily cleared a prolonged DTH response can occur
Prolonged DTH Response can lead to Granulomas:
- Continuous activation of macrophages:
1. Macrophages adhere to each other
2. Fuse to form multinucleated giant cells
3. Form palpable nodules
4. Release lytic enzymes
5. Tissue Damage
Eg. Mycobacterium tuberculosis in the lung
describe the autoimmune cause of Grave’s disease
– antibodies against hormone receptor
– activate the receptor
– Uncontrolled hormone production
- enlarged thyroid
describe the autoimmune cause of Myasthenia gravis
– Antibodies against acetylcholine receptor
– Act as an antagonist
– Block binding to receptor
– Severe muscle weakness
– Difficulties chewing, swallowing, breathing
– genetic component HLA-DR3 alleles
describe the cause and features of Systemic Lupus Erythematosus (SLE) - LUPUS
• Chronic, multiorgan disease
• Affects predominantly women
• Characterised by production of autoantibodies
against self DNA/RNA complexes
• Symptoms a result of DNA/ or RNA/Ab complexes
forming and triggering acute inflammation: type III
hypersensitivity
Features:
- Fever, weakness, arthritis, skin rashes, pleurisy, kidney dysfunction, etc.
- Autoantibodies to DNA, histones, RBCs, platelets, leukocytes and clotting factors
- RBCs & platelet autoantibodies lead to complement- mediated lysis of cells causing anaemia and thrombocytopenia
- Accumulation of immune complexes can be deposited along walls of small blood vessels which leads to type III hypersensitivity reaction
- why you see a rash forming
- Activates complement system - leads to tissue damage
describe Multiple Sclerosis (MS)
how is it linked to hypersensitivity and autoimmunity
Cell-mediated autoimmunity (Type IV hypersensitivity)
• Cell mediated immune attack in Central Nervous
System (CNS)
• Destruction of myelin and axons
• Central role for CD4+ helper T cells
• Self antigen = peptides of myelin - that’s the thing the cells attack
• Targets: myelin, oligodendrocytes, axons
• Numerous cells cause actual damage; prominent
role for macrophages, cytotoxic T cells
- not really known what started it ie why the body starts destroying its myelin and axons
what treatments are available for autoimmune diseases
no cure
- Immunosuppression - dampen type 2/3 hypersensitivity
- Immunomodulation - dampen type 2/3 hypersensitivity
- Plasmapheresis - clear blood of autoantibodies if there’s an exasberation
- IVIg - artificially introducing antibodies to individuals
- Protection of target - if its bound to a particular cell
- Autologous stem cell transplantation - clear body of T cells and give them new immune system - in extreme cases and need correct donor
- Tolerance induction / T cell vaccination (in trial) - more experimental
what treatments are available for autoimmune diseases
no cure
- Immunosuppression - dampen type 2/3 hypersensitivity
- Immunomodulation - dampen type 2/3 hypersensitivity
- Plasmapheresis - clear blood of autoantibodies if there’s an exasberation
- IVIg - artificially introducing antibodies to individuals
- Protection of target - if its bound to a particular cell
- Autologous stem cell transplantation - clear body of T cells and give them new immune system - in extreme cases and need correct donor
- Tolerance induction / T cell vaccination (in trial) - more experimental
can also treat the symptoms in organ-specific disorders
Explain the five cardinal signs of inflammation
- rubor (redness) - due to increased vascularity
- tumor (swelling) - exudation of fluid
- calor (heat) - increased blood flow and release of inflammatory mediators
- dolor (pain) - stretching of pain receptors and nerves by inflammatory exudates and by the release of chemical mediators
- functio laesa (loss of function) - combination of all of the above
Describe the events that occur during acute inflammation
- Local cells move towards site - mast cells and macrophages
- these release chemical signals
- causes things like increased blood flow
- phagocytic cells move in from capillaries to site
- phagocytosis occurs
Discuss possible outcomes of acute inflammation
Acute inflammation: relatively short duration (hours to
days): exudation of fluid and plasma protein, neutrophil
and monoctye infiltration
can result in good things:
- Complete resolution ( back to normal)
- Healing ( fibrosis)
but also sometimes bad things:
- Abscess formation
- Progressing to chronic inflammation
describe the three manners in which cytokines can work
Autocrine: Cytokine binds
to receptor on cell that
secreted it
Paracrine: Cytokine binds to
receptors on nearby cells
Endocrine: Cytokine binds
cells in distant parts of the
body
Give examples of cytokines which are Pro-inflammatory
IL- 1 TNF alpha IL-6 IL-8 IL-12
Give examples of cytokines which are Anti-viral
interferon α/B
what is the difference between the innate response and adaptive response of the immune system
Innate:
- rapid
- non-specific
- first line of defence
- not enhanced by repeated exposure
Adaptive:
- slow
- specific
- second line of defence
- enhanced by repeated exposure
describe the two types od adaptive immunity
• Humoral immunity
– Immunity that is mediated by antibodies
– Can be transferred by to a non-immune recipient by serum
• Cell Mediated Immunity
– Immune response in which antigen specific T cells dominate
describe Common Variable Immune Deficiency (CVID)
– Primary Immune Deficiency – Can occur at any age • Reduction in IgG, IgA and/or IgM • poor response to vaccines • defined causes of hypogammaglobulinaemia have been excluded
• CVID is an umbrella term for patients with
antibody deficiency in whom:
– no other primary cause is identified
– no secondary cause for the antibody deficiency has been identified
describe treatment of antibody deficiency
• sIgA deficiency often needs no treatment • Immunoglobulin replacement therapy (IRT) • Chest management • Prophylactic antibiotics • Disease specific complications – Autoimmune complications may require immunosuppressive therapy e.g haemolytic anaemia in CVID
describe SCID presentation, laboratory abnormalities, management
clinical presentation: • Infancy • Infections – Bacterial – Viral – Fungal • Failure to thrive
Laboratory abnormalities :
• lymphopaenia
• +/- hypogammaglobulinaemia
• Absent T cells or non functioning T cells (depending on the type, they may have absent B and or NK cells)
Management: • Isolation • Antimicrobial therapy • Immunoglobulin replacement • Talk to the transplant centre: BMT/stem cell therapy for definitive management
what are the functions of the complement system
- makes bacteria more susceptible to phagocytosis
- directly lyses some bacteria and foreign cells
- produces chemotactic substances - mediates inflammation
- increases vascular permeability
- causes smooth muscle contraction - promotes mast cell degranulation
describe the pathology of RSV bronchiolitis and pneumonia
• Pathology – Necrosis and sloughing of small airway epithelium – Oedema – Increased mucus secretion • Obstructs airflow in small airways – Interstitial infiltration – Alveolar filling
• Clinical
– Hyperinflation
– Atelectasis (collapsed lung)
– Wheezing
describe RSV pathogenesis
• Virus replication triggers immune response in
lungs
– Cytokine/chemokine release
– Infiltration of …
• neutrophils
• lymphocytes
• eosinophils
– Perivascular and peribronchiolar cuffing
– Trapping of air in lower lungs
• lung hyperinflation
• Once the immune response is triggered,
removal of RSV will not stop the pathogenesis
What is sepsis and septic shock?
• Sepsis
– The presence of SIRS associated with a confirmed infectious process.
• Severe sepsis
– Sepsis with either hypotension or systemic
manifestations of hypoperfusion
• Lactic acidosis, oliguria, altered mental status
• Septic shock
– Sepsis with hypotension despite adequate fluid
resuscitation, associated with hypoperfusion abnormalities
describe Systemic inflammatory response syndrome (SIRS)
2 or more of following symptoms:
• Temperature >38ºC or <36ºC
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min or PaCO2 of <32 mmHg
• White blood cell count >12,000 cells/mm3, <4000
cells/mm3, or >10% immature forms
what treatments are available for type 1 hypersensitivity reactions
Environmental – Avoid “it”
Pharmacologic:
- Anti-histamines – Blocks H1 and H2 receptors
- Cromolyn Chloride – Blocks mast cell degranulation if taken before allergen exposure (Nasodex)
- Corticosteroids – Blocks biosynthesis of histamines and arachidonic acid (leukotrienes and prostaglandins)
- Theophylline – Blocks degranulation through cAMP prolongation
- Epinephrine – Counteracts the effects of anaphylaxis shock
Immunological:
- Hypo or desensitization – Inject with increasing doses of antigen over time; induces IgG Abs to clear antigen prior to IgE binding
- Humanized Anti-IgE Antibodies – Binds to IgE in serum and used for asthma treatment (Xolair) – £6-18k per year
give some examples of organ-specific autoimmune diseases
type 1 diabetes
goodpasture’s syndrome
multiple sclerosis
- graves’ disease
- Hashimoto’s thyroiditis
- autoimmune pernicious anemia
- autoimmune Addison’s disease
- vitiligo
- myasthenia gravis
give some examples of systemic autoimmune diseases
rheumatoid arthritis
scleroderma
- systemic lupus erythematosus
- primary sjögren’s syndrome
- polymyositis
what are cytokines
Cytokines are small peptides that are usually
produced and secreted by the cells of the immune
system
Monokines: produced by mononuclear phagocytes:
monocytes
Lymphokines: produced by lymphocytes
Lymphokines and monokines – collectively
CYTOKINES
Cytokines act as a messenger between cells
many cytokines are known as interleukins:
cytokines made by one leukocyte and acting on other leukocytes.
what is the function of interleukin-2
Interleukin-2 (IL-2) is produced following T cell activation by antigen presenting cells. This cytokine acts in an autocrine loop to induce T cell proliferation
The major autocrine growth factor for T cells.
IL-2 (and IL-15) stimulates NK cell cytolytic function.
Acts on B cells as a growth factor.
Induces the death of activated T cells
IL-2 receptor has 3 chains IL-2Rαβγ. The α chain is the
cytokine specific chain and the γ chain is shared by a
number of cytokine receptors
what is the function of Interleukin-4
Interleukin-4 (IL-4) is a Th2 derived cytokine that stimulates B cell proliferation
what is the function of interleukin-17
Interleukin-17 (IL-17) is produced by activated T Helper 17 (Th17) cells
Is a major pro-inflammatory cytokine
what is the function of Tumour Necrosis Factor-α (TNF-α)
Principle mediator of the anti-bacterial response
what is the function of Transforming Growth Factor ( TGF)-β
TGF-β generally suppresses lymphocyte function
what is the function of interleukin-10
IL-10 generally suppresses the immune system
what is the major function of chemokine
act as a chemoattractant to guide the migration of cells
what is chemotaxis
Migration of cells along a chemical gradient
