Immune system Flashcards
Life is an arms race as…
…species compete for resources- both parties are evolving but one party can evolve MUCH faster
Types of extracellular worms?
Guinea worm
Hook worm
(Humans become infected with humans and animal worms)
WHat are multicellular eukaryote worms known as?
helminths
Types of Protozoa?
1) Plasmodium spp
- Malaria
- Resistance develops in endemic regions
2) Leishmania spp
- Leishmaniasis
- Found worldwide, including europe.
Type of fungi infection?
1) Candida albicans
- Oral candidiasis
2) Dermatophyte infection
- Ring worm
- Found worldwide
- Tinea pedis
- Tinea corporis
Tinea corporis affects…
…arms and legs
Tinea pedis affects…
… feet (athletes foot)
Candidiasis can affect…
…genital regions
Types of bacterial infection?
1) Staphylococcus aureus
- Impetigo
- Usually occurs after a cut / burn
- Very common in school children
2) Syphillis
- Treponema
- Sexually transmitted
Types of viruses?
1) Epstein-Barr virus
- Herpesviridae
- Infectious mononucleosis
- Usually acquired in childhood
- Later infection can be more severe
2) Mumps virus
- Paramyxoviridae
- Included in UK vaccination schedule
- Causes pain and swelling of salivary glands
Why we need an immune system
- To recognise ‘self’ that is damaged or altered
- Altered self can indicate the cell is dying or likely to become cancerous
- The immune system recognises this and destroys it
Pathogens have diverse infection methods and lifecycles which vary in…
- Complexity (multicellular vs viruses)
- Infection route (skin contact/sexually transmitted/airborne)
- Pathogenicity (fatal in all cases vs only symptomatic if immunocompromised)
- Location of infection (intracellular/extracellular)
The mammalian immune system can be split into …
…two branches (innate and adaptive)
Speed of innate immune system?
Rapid or instant
innate immune system is comprised of…
…physical and cell based mechanisms
Speed of adaptive immune system?
Slower to have effect
The adaptive immune system forms…
…‘memory’ of previous pathogens
What branch of the immune system is effective at birth?
innate
What branch of the immune system is ineffective at birth?
adaptive
The innate immune system does not involve what?
Specific recognition of a microbe
What does the innate immune system act against?
Acts against all microbes in the same way (targets common components of pathogens (PAMPs and DAMPs).
What does the adaptive immune response involve?
Involves specific recognition of a microbe
The adaptive immune response involves a specific ___ to a specific ___
The adaptive immune response involves a specific response to a specific microbe (targets unique components of pathogens)
The adaptive immune response produces cells which respond to…
…everything
Produces cells which respond to EVERYTHING! Then deletes the cells which …
…would damage healthy self
Whats the first line in innate immunity?
1) Physical barriers
Types of physical barriers?
- Skin
- Intact mucous membranes
Cells of the immune system have…
… specific-complementary roles
Whats the 2nd line of defence?
Antimicrobial substances / processes / cells
How does the 2nd line of defense work?
- Inflammation- increased blood flow to sites of damage allows increased numbers of immune cells to infiltrate tissue
- Fever
- Leukocytes (white cells)
Adaptive Immune system recognises…
…specific components of antigens
Where does the word antigen come from?
antibody generator
The adaptive immune system makes us of …
…lymphocytes
Our immune system prevents us from…
…getting viruses
Infection rates are much higher when the immune system is …
…compromised or immature
Many infections only occur when there is an…
…‘opportunity’ due to a specific factor
Pathogens have evolved ways of…
…evading the immune system
Some infections are cleared completely without …
…symptoms
Some infections are cleared after…
… a symptomatic period
Some infections are …
…persistent.
The adaptive immune system can learn from …
…experience.
The adaptive immune system can learn from experience.
- Sometimes this prevents …
…re-infection giving us immunity
The adaptive immune system can learn from experience.
- Sometimes this prevents re-infection giving us immunity.
- Or the infection is less …
…severe the second time / recover much faster
Three main functions of cells of the immune ystem?
1) direct killing of pathogen-by phagocytosis or release of cytotoxic agents
2) releasing chemicals (cytokines and chemokines) to recruit other immune cells
3) Activating T-cells by presenting foreign antigen to them (antigen presenting cells)
Innate immune cells respond in the ____ when triggered by signals which are not ____ for a particular pathogen.
Innate immune cells respond in the same way when triggered by signals which are not specific for a particular pathogen.
What can innate immune cells be activated by?
antibodies (immunoglobulins) or by contact with PAMPs or DAMPs
How do innate immune cells kill?
By degranulation or phagocytosis
What are the Innate immune cells?
- Neutrophils
- Eosinophils
- Basophils
- Mast cells
- Monocytes
- Macrophages
- Natural killer cells
- Dendritic cells
What do some innate immune cells release?
Chemicals to recruit other immune cells or increase vascular permeability
What do some innate immune cells present?
antigen to T cells
Function of neutrophil?
Phagocytosis and killing of microorganisms
Describe the nucleus of neutrophils?
Multilobed nucleus
Function of small lymphocyte?
Production of antibodies (B cells) or cytotoxic and helper functions (T cells)
What is a plasma cell?
Fully differentiated form of B cell that secretes antibodies.
Function of natural killer cells?
Kills cells infected with certain viruses.
Function of dendritic cell?
Activation of t cells and initiation of adaptive immune responses?
Function of monocyte?
Circulating precursor cell to macrophage
Function of macrophage?
- Phagocytosis and killing of microorganisms.
- Activation of t cells and initiation of immune responses.
Function of eosinophils?
Killing of antibody-coated parasites through release of granule contents.
Function of basophil?
Promotion of allergic responses and augmentation of anti-parasitic immunity.
Function of mast cell?
Expulsion of parasites from body through release of granules containing histamine and other active agents.
What are the commonest leucocyte?
Neutrophils
Neutrophils contain…
…granules full of numerous bactericidal substances (targets bacteria)
Neutrophils avidly…
…phagocytoses particles
Neutrophils bind avidly to which antibodies?
IgG antibodies which have bound to a pathogen (opsonisation).
WHat are IgG antibodies made by?
B cells.
How do neutrophils destroy pathogens?
engulfs the pathogen and destroys it
Eosinophils are a type of …
… leucocyte (white blood cell)
Eosinophils stain with…
…acidic dyes
Eosinophils make up…
…1-6% of white blood cells.
Eosinophils contain…
…a number of highly basic or ‘cationic’ proteins (antimicrobial).
Eosinophils are important in…
…killing larger multi cellular pathogens
Eosinophils are abundant as sites of…
…allergic reactions.
Eosinophils bind avidly to…
…IgE antibodies which are bound to exterior pathogens
Where are IgE antibodies released?
released at mucous membranes
Eosinophils are involved in…
…parasitic infections eg: helminths
In a helminth (worm) infection, eosinophils are attacking…
…a schistosome larva.
How important is schistomiasis?
After malaria 2nd most important tropical disease
Pathology of schistosomiasis caused by…
…human immune system-over reaction causes excessive inflammation
Basophils are leucocytes with…
…large granules that stain with basic dyes
The granules of basophils contain…
- Heparin
- Histamine & other vasoactive amines (cause vasodilation and increased permeability of blood vessels)
- This why the condition will be itchy
Granules of basophils are released at…
…sites of inflammation.
Basophils released granules in…
…immediate hypersensitivity (allergic) reactions
Basophils bind to …
…IgE antibodies that have bound antigen
Basophils bind to IgE antibodies that have bound antigen.
- Then release…
…basophil granules
Mast cells are a …
…tissue cell
Mast cells are similar to…
…its circulating counter part, the basophil.
Upon stimulation, mast cells rapidly release…
…inflammatory mediators (recruiting other immune cells)
Monocytes are the largest…
…nucleated cell of the blood.
Size of monocytes?
16-20mm diameter
Monocytes develop into…
…macrophages when it migrates into the tissues.
What are macrophages?
A professional antigen presenting cell (APC)-presents antigen to T cells
Macrophages are the principal…
…resident phagocyte of the tissues.
Macrophages are strongly…
…phagocytic of particles and microbes
Phage means…
…eating
Macrophages have receptors for…
…antibodies
Types of macrophages?
CNS – “microglia”
Liver – “Kupffer cells”
Lungs – “alveolar macrophages”
Bone – “osteoclasts”
Natural killer cells (NK cells) are a type of…
…lymphocyte
Natural killer cells are a type of lymphocytes which recognises…
…‘self’ cells that have something wrong with them
NK cells are able to kill…
…infected cells.
NK cells kill…
…certain type of cancer cells.
NK cells act independantly of…
…antigen presentation and recognition events required for cytotoxic T cell killing
NK cells are microscopically distinguishable by…
- Presence of large cytoplasmic granules
- Large granular lymphocytes
Dendritic Cells possess…
…long processes
Dendrites means…
…fingers
Dendritic cells have…
…membranous projections
Dendritic cells have membranous projections which interlock with…
…lymphoid cells.
Dendritic cells present…
… antigen to T cells- activating the T-cell
Two types of dendritic cells…
1) Plasmacytoid DCs
2) Conventional DCs (aka myeloid DCs)
Plasmacytoid DCs are found in…
…germinal centres within the lymph nodes
Plasmacytoid DCs produce…
…huge amounts of type I interferon
Conventional DCs (aka myeloid DCs) are present in…
…most organs.
Conventional DCs (aka myeloid DCs) are abundant in…
…t-cell-rich areas of spleen and lymph node.
Conventional DCs (aka myeloid DCs) present…
…antigen to T-cells.
Role of dendritic cells in innate immunity?
- Phagocytic cells
- Like other cells they recognise pathogens through surface receptors and become ‘activated’
Role of dendritic cells in adaptive immunity?
- Phagocytise pathogens and display their antigen (presentation)
- This activates the T & B cells
B cells and T cells are…
…Adaptive immune cells.
B cells and T cells are Adaptive immune cells. They have a …
…receptor for a specific epitope (one particular part of the antigen).
B cells and T cells proliferate (clonal expansion) when …
…they encounter their antigen. Some of these cells will be long lived memory cells.
B cells produce…
…antibodies, as surface receptors or secreted proteins (BCR)
B cells produced how many classes of antibodies?
Five classes of antibody
B cells recognise…
…extracellular pathogens.
B cells are important for…
…passive immunity (eg. antivenom, breastmilk)
T cells bear a …
… T cell receptor (TCR)
T cells recognise…
…intracellular pathogens or malignant cells
T cells only recognise antigens that have been…
…presented by an antigen presenting cell (APC)
Size of T lymphocytes?
6-15μm diameter
Two main subdivisions of T lymphocyte?
- CD8 (cytotoxic T cells / Tc) – Kill infected cells / cancer cells
- CD4 (helper T cells / Th) – Activate macrophages & Tc Cells
B lymphocytes are derived from…
…bone marrow
B Lymphocytes transform into…
… a plasma cells.
A plasma cell is a lymphocyte in its…
…high-rate antibody secreting state
Plasma cells are rarely seen in the…
…blood
Plasma cells are found in…
…the spleen and lymph nodes.
Plasma cells release…
…antibodies into circulation.
The lymphatic system is a network of…
…vessels
The lymphatic system conveys…
…extracellular tissue fluid
The lymphatic system conveys extracellular tissue fluid as lymph via…
…the thoracic duct, back to the bloodstream.
the lymphatic system consists of…
…fine, blind-ended lymphatic capillaries
The lymphatic system consists of fine, blind-ended lymphatic capillaries…
…which unite to form lymphatic vessels
- Vessels have valves to prevent backflow of lymph
The lymphatic system has…
…3 primary functions.
3 primary functions of the lymphatic system?
1) Drains excess interstitial fluid – Lymphatic vessels drain excess interstitial fluid from tissue spaces and return it to the blood
2) Transports dietary lipds – Lymphatic vessels transport lipids and lipid soluble vitamins (A, D, E & K) absorbed by the gastrointestinal tract
3) Carries out immune responses – Lymphatic tissue and lymphoid organs initiate a highly specific responses directed against particular microbes
At various points along the vessels of the lymphatic system are…
…lymph nodes.
where are lymph nodes located?
under arms, groin, neck.
Lymph is similar in composition to plasma.
But contains…
- Less protein
- Some cells (mainly lymphocytes)
Appearance of lymph?
- Milky in appearance.
When lymphatic vessels become inflamed they can sometimes be seen as …
…red streaks in the skin (lymphangitis).
WHats blockage of the lymphatic system called?
- Lymphatic filariasis
- Elephantiasis of the legs and scrotum
The Lymphoid Organs:
Bone Marrow
Thymus
Lymph nodes
Spleen
Adenoids and tonsils
Gut associated lymphoid tissue
Primary lymphoid organs?
- Bone marrow
- Thymus
Secondary lymphoid organs?
- Adenoids
- Tonsils
- Lymph nodes
- Spleen
- Peyer’s patches
- Appendix
Bone marrow makes up…
…about 4% of an adult’s body mass
Bone marrow is the major …
…haemopoietic organ
Bone marrow is responsible for…
…formation of blood cells
- Includes red & white blood cells
Bone marrow releases…
…500 billion blood cells a day
Bone marrow is primarily found in…
…cancellous (spongy) bone
cancellous (spongy) bone is different to…
…compact (cortical) bone which is involved in support
Spongy bone is highly…
…vascularised
Where is cancellous spongy bone found?
Found at the ends of the long bones
Examples of Cancellous bone?
Femur / Humerus / Tibia
Example of flat bones?
Pelvis
Sternum
Cranium
Ribs & Vertebrae
Scapulae
T cell precursors are called…
…thymocytes
T cell precursors migrate from…
…the bone marrow to the thymus to mature.
Mature T cells leave the…
…thymus and migrate to secondary lymphatic tissues.
Mature T cells leave the thymus and migrate to secondary lymphatic tissues, where they may encounter…
…foreign antigen
Where is thymus located?
- Upper thorax
- Above the heart
- Behind the sternum
Haematoxylin/eosin stained is made up of…
…many lobules
Haematoxylin/eosin stained is surrounded by…
… a capsule
Haematoxylin/eosin stained contain a…
…cortex / medulla
Haematoxylin/eosin stained between lobules is a…
…septa
SEM showing the …
…developing thymocytes
Within the thymus there is…
…spherical cells.
What is the interstices?
An extensive network of epithelial cells
The thymocytes are dependent on …
.. the epithelial cells during development
What do the lobules of the thymus show?
- A lymphocyte dense outer cortex
- An inner lighter-staining medulla
The thymus has a…
…stromal framework
The thymus has a stromal framework with…
…specialised epithelial cells (dendritic cells and macrophages (APCs)).
Role of the thymus in the adaptive immune response?
Produces cells which respond to EVERYTHING! Then deletes the cells which would damage healthy-self
role of cortex and medulla of thymus?
“educates” thymocytes.
Cortex and medulla ‘educate’ thymocytes, causing them to become…
… mature competent T cells
What percentage of T cells survive ‘education’ ?
1 to 3%
Only 1 - 3% of T cells survive education, so theres massive ____ of the other cells.
Only 1 - 3% of T cells survive education, so theres massive apoptosis of the other cells.
Only 1 - 3% of T cells survive education, so theres massive apoptosis of the other cells.
How do they die?
Macrophages phagocytose them without any concurrent inflammation.
Mature T cells that aren’t dangerous to host tissue are released into the …
…peripheral circulation
Mature T cells that aren’t dangerous to host tissue are released into the peripheral circulation.
Via….
… thymic medullary venules
What is Thymic atrophy with age?
- Fewer naïve (new, haven’t encountered antigen) T cells produced with increasing age
- Reducing mass and function
What is thymic atropy with age responsible for?
Responsible for poor responses of older people to flu vaccination.
Which organ is the site of haematopoesis? Bone marrow or Thymus?
Bone marrow
Which organ…Is the site of T-cell maturation?
Bone marrow or thymus?
Thymus
So the primary lymphoid organs are the …
…bone marrow and thymus which make mature immune cells.
What is the role of secondary lymphoid tissues?
They are tissues where lymphocytes come into contact with foreign antigens
What happens to lymphocytes when they come into contact with foreign antigens in the secondary lymphoid tissues?
- Cells are clonally expanded (divide repeatedly while maintaining their specificity).
- Mature into effector cells.
- Eg. lymph nodes and the spleen, MALT, NALT, BALT, and GALT
T and B lymphocytes are unique in constantly recirculating between…
… blood and tissues
T and B lymphocytes are unique in constantly recirculating between blood and tissues
- Returning to blood via…
…lymph and secondary lymphoid tissue.
Secondary lymph tissues enable…
…thorough mixing of T and B lymphocytes with Antigen Presenting Cells (APCs), especially those that may have recently encountered foreign antigens.
- Providing maximum contact.
What are APCs?
Antigen Presenting Cells
Without 2o lymphoid tissues this contact would otherwise be …
… a rare event.
Lymph nodes have an internal framework of …
…reticular fibres (type III collagen)
Lymph nodes have an internal framework of reticular fibres (type III collagen).
These reticular fibres are suited to the attachment of…
…abundant lymphocytes, macrophages, and dendritic cells.
What is a Germinal Centre?
A spherical aggregation of B lymphocytes and lymphoblasts.
- Together with follicular dendritic cells
- Macrophages and a few CD4+ T cells.
Germinal centres develop in …
…primary follicles of lymphoid tissues - becomes a secondary follicle.
Development of germinal centres requires what?
Requires T-cell interaction.
Small oligoclonal foci of activated B cells develop into…
…germinal centres
What happens to B cells of germinal centres?
1) The B cells proliferate rapidly, doubling every 6-12 hours
2) Transform in plasma / memory cells
3) Are modified to recognise antigen better
Germinal centres produce?
1) Plasma cells
2) Memory cells
What are plasma cells?
A type of B cell, making antibodies.
Plasma cells do not…
…circulate in the blood
Plasma cells do not circulate in the blood but…
… migrate to bone marrow, red pulp of spleen or deep cortex of lymph node.
Memory cells circulate in…
… the blood.
Memory cells are long what?
…long lived
Memory cells set up…
…new germinal centres upon next exposure to antigen.
Memory cells allow for a …
… faster response
The 3 main types of professional Antigen Presenting Cell (APC) are…
1) Dendritic cells
2) Macrophages
3) B Cells
Function of the 3 main types of professional Antigen Presenting Cell (APC)?
present antigen to T-cells
The 3 main types of professional Antigen Presenting Cell (APC) are all found in the…
…lymph node.
The spleen contains …
…25% of the total lymphocytes of the body.
Splenectomised patients are …
… immunocompromised
Splenectomised patients are immuno-compromised.
- Especially to…
…infection by encapsulated bacteria such as pneumococci.
Splenectomised patients are immuno-compromised and so must be….
…vaccinated because a simple infection can cause sepsis.
Unlike lymph nodes the spleen does not …
…receive lymph
Unlike lymph nodes the spleen does not receive lymph.
It contains…
…many red blood cells.
Red pulp in the spleen is…
…sponge like
Red pulp of the spleen consists of…
… blood sinuses
Red pulp of the spleen has cords of…
…reticular meshwork
What white blood cells does the red pulp of the spleen contain?
Plasma cells and macrophages
Red pulp of the spleen is responsible for…
…mechanical filtration of the blood
Ultimate function of the Red pulp of the spleen?
To eliminate aged and abnormal erythrocytes and platelets
What are the two different pulps of the spleen?
1) Red pulp
2) White pulp
Where is the red pulp and white pulp found?
The Spleen
What does white pulp contain?
Peri arteriolar lymphoid sheaths (PALS)
What is white pulp largely populated by?
Largely populated by T cells
White pulps are …
… germinal centres.
White pulp is rich in…
… B lymphocytes
What is the function of white pulp?
Active immune response through humoral and cell-mediated pathways
Which organ…Allows the interaction of foreign antigen in lymphatic fluid with numerous B and T cells?
Spleen or lymph nodes?
Lymph nodes.
Which organ…Allows the interaction of foreign antigen in blood with numerous B and T cells?
Spleen or Lymph nodes?
The spleen
What is MALT?
Mucosa Associated Lymphoid Tissue (MALT)
The main entry sites into the body are …
…the mucosal surfaces
The main entry sites into the body are the mucosal surfaces.
These are protected by…
…Specialist tissues.
What is a tonsil?
Mass of lymphoid tissue in submucosa of oropharynx
What are tonsils made up from?
Many lymphoid follicles, mostly with germinal centres
