ICS - Immunology Flashcards
Haematopoiesis starts with…?
Multi potential hematopoietic stem cell (hemocytoblast)
What do hemocytoblasts differentiate into?
- Common myeloid progenitor
- Common lymphoid progenitor
What do common myeloid progenitors differentiate into?
- Megakaryocytes (—> thrombocytes)
- Erythrocytes
- Mast cells
- Myeloblast (—> basophil, neutrophil, eosinophil, monocyte (—> macrophage))
What do common lymphoid progenitors differentiate into?
- Natural killer cell
- Small lymphocyte (—> T lymphocyte, B lymphocyte (—> plasma cell))
Describe innate immunity
- Rapid and non-specific defence system
- Present from birth
- Focused around physical and chemical barriers
- No lymphocyte involvement
Give examples of physical and chemical barriers used in innate immunity
Skin, mucociliary escalator, gastric acid, hairs, lysozymes
What do lysozymes do?
Destroys bacterial cell walls
When do monocytes become macrophages?
When they migrate from blood to tissue
Describe the role of neutrophils
Phagocytosis and bactericide
Describe the role of macrophages
Phagocytosis, antigen presenting and cytokine secretion
Describe the role of basophils
Secrete histamine and heparin in allergic reactions, eczema, hayfever etc.
Describe the role of eosinophils
Release cationic granules in parasitic infections
Describe the role of mast cells
Release histamines when IgE binds to them during anaphylaxis and asthma (type 1 hypersensitivity reactions)
Describe the role of natural killer cells
Release lytic granules that kill virus infected cells
Describe the role of dendritic cells
Antigen presenting cells that reside in the epithelium (liver = kupffer, skin = langerhans)
Describe the role of antigen presenting cells
Process and present antigens from pathogens for recognitions
What are the main antigen presenting cells (considered ‘professional’ at activating lymphocytes)?
Dendritic cells (also macrophages and B cells)
How are bacteria/fungi destroyed?
Phagocytosis
How are viruses destroyed?
Cellular shutdown/resistance and apoptosis
Which leukocytes are polymorphonuclear?
Neutrophils, basophils and eosinophils
Which leukocytes are mononuclear?
Monocytes, B lymphocytes and T lymphocytes
Where do T cells mature?
Thymus
Where do B cells mature?
Bone marrow
How do T cells recognise antigens?
T cells cannot recognise soluble antigens. Antigens must be displayed by an APC and bound to MHC1/2 in order to be recognised
What do pattern recognition receptors (PRRs) include?
Chemoattraction of leukocytes and phagocytosis
What are pattern recognition receptors (PRRs)?
Receptors on cells that bind to PAMPs on microbes. They recognise patterns that belong to non-self organisms
PRRs and PAMPs are associated with what kind of immunity?
Innate immunity
What are toll-like receptors?
A class of PRRs that recognise both invading pathogens and endogenous molecules released from dying cells and damaged tissue (DAMPs). Send signals to the nucleus to secrete cytokines and interferons
What does TLR2 recognise?
Foreign substances
What does TLR4 recognise?
Gram-negative lipopolysaccharide
What does TLR5 recognise?
Flagellin
What does TLR7 recognise?
Single-stranded RNA
What does TLR9 do?
Binds DNA present in bacteria/viruses and triggers signalling cascade that lead to a pro-inflammatory cytokine response
Where are complement system plasma proteins derived from?
The liver
What are the 3 main outcomes of the complement system activation?
- Opsonisation (C3b and C4b) - increased phagocytosis
- Chemotaxis (C3a and C5a) - attracts and activates leukocytes
- Direct lysis (C5 to C9) - kill cell directly
What are the 3 pathways of the complement system?
- Classic
- Alternative
- Lectin
What activates the classic pathway of the complement system?
Antibodies
What activates the alternative pathway of the complement system?
Bacterial cell walls and endotoxin
What activates the lectin pathway of the complement system?
Mannose binding protein
What are pathogen associated molecular patterns (PAMPs)?
Patterns/structures of molecules found on microbes, specific to microbes
Give 4 examples of pathogen associated molecular patterns (PAMPs)
- Flagellin - protein found in bacterial flagella
- Lipopolysaccharide (LPS) - found in outer membrane of gram-negative bacteria
- Peptidoglycan - found in bacterial cell walls
- Lipoarabinomannan - mycobacteria
What happens when a PAMP binds to a PRR?
The innate immune response and inflammatory response is triggered
Define adaptive immunity
Specific acquired defence system. Has a memory and quicker response
What is the function of T helper 1 (CD4)?
Involved in cell-mediated immunity (response against intracellular pathogens). Regulates monocytes and macrophages and secretes cytokines. Secrete interferon gamma which causes cells to undergo apoptosis
What is the function of T helper 2 (CD4)?
Involved in humoral immunity (response against extracellular pathogens). Regulates eosinophils, basophils and mast cells and secretes cytokines. Binds to B cells and triggers them to divide
What is the function of T reg?
Regulates immune response
What is the function of Th17?
Protection against extracellular pathogens. TH17 cells produce transcription factors and cytokines that suppress T reg cells
What is the function of cytotoxic T cells (CD8)?
Bind to antigens and release perforin (causes cell lysis) and granzymes (induces apoptosis). Also secrete molecules that stop neighbouring cells from become infected and pro-inflammatory molecules/chemokines that attract other immune cells to the site of infection
What is the function of B cells?
Become plasma cells which secrete antibodies
Give 3 functions of antibodies
- Neutralise toxins
- Opsonisation
- Activate classic complement system
What are the 5 main antibodies?
IgA, IgM, IgG, IgE and IgD
Describe IgA
- Found in colostrum (breast milk) and coats noenate gut
- Found in mucous membranes (resp/digestive tract), saliva and tears
Describe IgM
- Found in blood and lymph fluid
- First antibody made when fighting a new infection
- Activates complement system
Describe IgG
- Found in blood (most abundant)
- Important during secondary response
- Can cross placenta (in utero protection)
Describe IgE
- Found in the blood (small amounts)
- Bound to mast cells and basophils
- Important in allergies
What are the two most common antibodies?
IgG and IgM
Describe primary immunodeficiency and give an example
- Born with intrinsic defects in the immune system
- Rare and mostly genetic disorders
- e.g. SCID (severe combined immunodeficiency)
Describe secondary immunodeficiency (a.k.a immunosuppression) and give an example
- Acquired
- Can be drug induced (e.g. steroids, azathioprine, chemotherapy)
- e.g. AIDS (acquired immune deficiency syndrome)
Describe type I hypersensitivity
- IgE mediated
-E.g. anaphylaxis - IgE binds to mast cells which leads to mast cell degranulation (release of histamine)
- Can be caused by allergies
Describe type II hypersensitivity
- IgG mediated cytotoxicity
- E.g. autoimmune haemolytic anaemia
- Can be caused by transplant rejection
Describe type III hypersensitivity
- Immune complex deposition
- Immune complexes not been adequately cleared
- Gives rise to an inflammatory response
- E.g. systemic lupus erythematosus
- Can be caused by fungal
Describe type IV hypersensitivity
- T cell mediated
- E.g. graft vs host disease, MS
- Can be caused by tuberculosis
Give 6 features of anaphylaxis
- Rapid onset
- Blotchy rash
- Swelling of face and lips
- Wheezing
- Hypotension
- Cardiac arrest (if severe)
Describe the general structure of an antibody
Fc region at base and two Fab regions (makes Y shape)
What is the function of the Fc region on an antibody?
Binds to Fc receptor on phagocyte/B cell to bring microbes in close proximity to WBCs
What is the function of the Fab regions on an antibody?
Bind to epitopes on antigens (on microbes). Variable regions
What are cytokines?
Small proteins that orchestrate and regulate an immune response. Can either be pro-inflammatory or anti-inflammatory
Name 4 types of cytokines
- Interferones (IFN)
- Interleukins (IL)
- Colony stimulating factors
- Tumour necrosis factors
Describe the role of interferons
Produce antiviral proteins that induce a state of antiviral resistance in uninfected cells
Describe the role of interleukins
Cause cells to divide, differentiate and secrete factors. Can be pro- (IL1) or anti-inflammatory (IL10)
Describe the role of colony stimulating factors
Cause division and differentiation of bone marrow stem cells (to make more leukocytes)
Describe the role of tumour necrosis factors
Mediate inflammation and cytotoxic reactions
What do chemokines do?
Attract leukocytes to sites of infection
Define extravasation
Migration of leukocytes from the circulation into tissues where infection is occurring
What is secreted at tissues to initiate extravasation?
TNF alpha by pro-inflammatory molecules (e.g. macrophages)
What does TNF alpha do?
- Causes surrounding cells to secrete chemokines (attract neutrophils)
- Causes endothelium to become sticky using adhesion molecules (neutrophils can stick)
Describe extravasation
- TNF alpha released
- Adhesion molecules and chemokines stimulated
- Neutrophils bind and start to roll
- Neutrophils become stuck to endothelium (adhesion molecules and integrins)
- Neutrophils migrate through endothelium into tissue
- Migrate up chemokine conc. gradient to site of infection
What is the function of major histocompatibility complex (MHC)?
Displays fragments from pathogens for recognition by T cells
Which cells express MHC1?
All nucleated cells
Which cells express MHC2?
Antigen presenting cells e.g. macrophages, dendritic cells, B cells
Intrinsic antigens are displayed by…?
MHC1
Extrinsic antigens are displayed by…?
MHC2
Which type of T cell binds to MHC1?
Cytotoxic T cells (CD8)
Which type of T cell binds to MHC2?
T helper cells (CD4)
What happens to T cells that recognise self?
Killed in utero
What are T cell receptors (TCRs)?
Receptors that recognise foreign antigens but only when displayed by MHCs
What is required for T cell activation?
CD28 on T cell must bind to CD80/CD86 on APC
What happens after a T cell binds to a T cell receptor?
IL-2 is secreted and binds to IL-2R on T cells. This produces a positive feedback mechanism of division and differentiation
What 2 routes can activated T cells take?
CD8 way or CD4 way (–> TH1 and TH2)
What happens to B cells that recognise self?
Killed in bone marrow
Define autoimmunity
The system of immune responses of an organism against its own health cells, tissues and other normal body constituents
When do we gain natural active immunity?
After exposure to antigens from pathogens in the environment
When do we gain artificial active immunity?
After being vaccinated
When do we gain natural passive immunity?
From maternal antibodies in colostrum
When do we gain active passive immunity?
After transfer of antibodies from one organism to another
Define negative phase
Period after initial antigen exposure where ones’ immunity is lower than before encountering the antigen
Compare active and passive immunisation
Active is more effective than passive and has a memory but has a lag period and negative phase which passive doesn’t
What is a live vaccine?
Live pathogen is injected
Give 2 examples of live vaccines
BCG (TB) vaccine and MMR vaccine
Give 3 advantages of live vaccines
- Effective, prolonged and comprehensive
- Immunological memory produced
- Usually only 1 vaccine needed
Give 2 disadvantages of live vaccines
- Infection may occur in immunocompromised patients
- Vaccines often needed to be refrigerated
What is an inactive vaccine?
Inactivated pathogen is injected
Give 2 advantages of inactivated vaccines
- No risk of infection
- Less difficulty to store
Give 2 disadvantages of inactivated vaccines
- Weaker response (humoral response - lack of T cell involvement)
- Boosters often needed
What is a subunit vaccine?
Only antigenic part injected
Give 1 advantage of subunit vaccines
Lower infection risk (safer)
Give 2 disadvantages of subunit vaccines
- Repeat jabs needed
- Adjuvants needed to produce a response
What is an adjuvant?
A substance added to a vaccination to stimulate an immune response (e.g. toxoid, proteins etc.). Convince the immune system that the body is infected
What is a DNA vaccine?
Gene from pathogen expressed in host cell to cause an immune response and lead to memory cell production
What is a recombinant vector vaccine?
Imitates effects of infection with pathogen using non pathogenic organism
What is a polysaccharide vaccine?
Composed of long chains of sugar molecules that make up the surface capsule of certain bacteria
What diseases can polysaccharides vaccines be used to treat?
- Pneumococcal disease
- Salmonella typhi
- Meningococcal disease
What are DAMPs?
Damage associated molecular patterns - endogenous molecules released by damaged or dying cells
