Intro to immunology Flashcards
What is the job of the immune system?
Must discriminate self from non-self
What is innate immunity?
Instinctive, non-specific, does not depend on lymphocytes, present from birth
What is adaptive immunity?
Specific ‘Acquired/learned’ immunity, requires lymphocytes, antibodies
What makes up both innate and adaptive immunity?
cells and soluble factors (humoral)
What are pluripotent haematopoietic stem cells?
the stem cell that every blood cell in the body originates from
What is the process of blood cells being formed?
Haematopoiesis
What determines which type of blood cell is formed in haematopoiesis?
Colony stimulating factors will drive the cells down different pathways
What are the 2 types of cells in the immune system?
Polymorphonuclear leukocytes and mononuclear leukocytes
What does polymorphonuclear mean?
It has more than 1 nuclei
Which cells are polymorphonuclear leukocytes?
Neutrophil
Eosinophil
Basophil
Which cells are mononuclear leukocytes?
Monocyte
T-cell
B-cell
What are features of neutrophils?
- 75% of WBC
- Short lived - 1 day
- Terminated in spleen
- Characteristic 3 interconnected nuclei
What do neutrophils do?
- Plays an important role in innate immunity (phagocytosis)
- 2 main intracellular granules
Primary lysosomes – can kill microbes by secreting toxic substances
Secondary granules
What do eosinophils do?
- Mainly associated with parasitic infections and allergic reactions
- Lifespan 8-12 days
- Granules stain for acidic dyes (eosin)
- Activates neutrophils, induces histamine release from mast cells and provokes bronchospasm
What do basophils do?
- Mainly involved in immunity to parasitic infections and allergic reactions
- Lifespan 2 days
- Granules stain for basic dyes
- Very similar to mast cells
- Binding of IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
What do mast cells do?
- Only in tissues (precursor in blood)
- Very similar to basophils
- Binding to IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
What are monocytes the precursor of?
Macrophages
What do T cells have a role in?
major role in adaptive immunity
Where do T cells mature?
Thymus
What do T cells do?
- Recognise peptide Ag displayed presenting cells (APC)
- Lifespan hours-years
- Found in blood, lymph nodes and spleen
What are the different types of T cell?
T helper 1 (CD4 – help immune response intracellular pathogens)
T helper 2 (CD4 – help produce antibodies extracellular pathogens)
Cytotoxic T cell (CD8 – can kill cells directly)
T regulator – regulate immune responses
What do B cells have a role in?
major role in adaptive immunity
Where do B cells mature?
Bone marrow
What do B cells do?
- Recognise Ag displayed by antigen presenting cells (APC)
- Differentiate into plasma cells that make antibodies
- Found in blood, lymph nodes and spleen
What are natural killer cells?
- Account for 15% of lymphocytes
- Found in spleen, tissues
What do natural killer cells do?
They recognise and kill by apoptosis;
- Virus infected cells
- Tumours cells
What do dendritic cells do?
- Patrol to see what crosses tissues
eg. - Kupffer - liver, langerhans - skin
What are soluble factors?
- Complement
- Antibodies
- Cytokines, Chemokines
What is complement?
- Group of ~20 serum proteins secreted by the liver that circulate inactivated and need to be activated to be functional
- Complement is activated only as part of the immune response
What are the 2 types of complement?
Classical – Ab bound to microbe
Alternative – C’ (complement) binds to microbe
What are the 3 modes of action by complement?
- Direct lysis
- Attract more Leukocytes to site of infection
- Coat invading organisms
What are antibodies (Ab) do?
Bind specifically to Antigens (Ag)
What are immunoglobulin’s?
Ig’s are glycoproteins
Soluble
What are the 5 classes of Ig’s?
- IgG (IgG1-4)
- IgA (IgA1 & 2)
- IgM
- IgD
- IgE
What are features of IgG?
- Most predominant Ig in human serum – 70-75%
- Crosses placenta
What are features of IgA?
- Accounts for 15% of Ig in serum
- Predominant Ig in mucous secretions such as saliva, colostrum, milk and bronchiolar secretions
What are features of IgM?
- Accounts for 10% of Ig in serum
- Mainly found in blood (they’re big so they can’t cross the endothelium)
- Mainly primary response, initial contact with Ag
- In an infection, IgM will go up first, then
IgG
What are features of IgD?
- Accounts for 1% of Ig in serum
- A transmembrane monomeric form is present on mature B cells (mIgD)
What are features of IgE?
- Accounts for ~0.05% of Ig in serum
- Basophils and mast cells express an IgE-specific receptor that has high affinity for IgE
- Basophils and Mast Cells are continually saturated with IgE
– binding triggers release of histamine - Associated with hypersensitivity allergic response and defence against parasitic infections
What is an antibody?
- protein produced in response to an antigen
- It can only bind with the antigen that induced its formation
What is an antigen?
- a molecule that reacts with preformed antibody and specific receptors on T and B cells
What is an epitope?
the part of the antigen that binds to the antibody/ receptor binding site
What is affinity?
measure of binding strength between an epitope and an antibody binding site
What is a cytokine?
- proteins secreted by immune and non-immune cells (WBCs, epithelial, endothelial cells)
- Substances produced by one cell that influence the behaviour of another, thus effecting intercellular communication
What are interferons? (IFN)
Induce a state of antiviral resistance in uninfected cells & limit the spread of viral infection
What are interleukins? (IL)
- Produced by many cells, over 30 types
- Can cause cells to divide, to differentiate and to secrete factors
What are colony stimulating factors? (CSF)
Involved in directing the division and differentiation on bone marrow stem cells – precursors of leukocytes
What are tumour necrosis factors? (TNFa & b)
- Mediate inflammation and cytotoxic reactions
- Pro-inflammatory
What are chemokines?
- Group of approx. 40 proteins that direct movement of leukocytes (and other cells) from the blood stream into the tissues or lymph organs by binding to specific receptors on cells
What are the 2 defence systems?
Innate (non-specific)
Adaptive (specific)
Describe innate immunity
- 1st line of defence
- Provides barrier to antigen
- Instinctive
- Present from birth
- Slow response
- No memory
- NO LYMPHOCYTES
Describe adaptive immunity
- Response specific to antigen
- Learnt behaviour
- Memory to specific antigen
- Quicker response
- REQUIRES LYMPHOCYTES
What are limitations of innate immunity?
- Effective but limited
- Can be evaded
- Primitive (spread across species)
- Instinctive response
- No long lasting memory
What does innate immunity consist of?
- Physical and chemical barriers
- Phagocytic cells (neutrophils and macrophages)
- Blood proteins (complement, acute phase)
What are some anatomical barriers?
- Skin: dermis and epidermis
- Sebum (skin secretions)
- Intact skin: prevents penetration, prevents growth
What are some physical barriers?
- Saliva
- Tears – lysozyme in tears and other secretions
- Low pH and commensals of vagina
- Mucous secretions
- Mucous – entrapment
- Cilia – beating removes microbes
- Commensal colonies – attachment, nutrients
What are some physiological barriers?
- Temperature – chickens have high body temperature and are Anthrax resistant
- Fever response inhibits micro-organism growth
- pH
- Gastric acidity – neonate stomach less acidic than adult so susceptible to infection
What are the hallmarks of innate immunity?
- Primitive (spread across species)
- ‘un-learned/instinctive’ response
- Does not depend on immune recognition by lymphocytes
- Does not have long lasting memory
- Integrates with Adaptive response
Define inflammation
a series of reactions that brings cells and molecule of the immune system to sites of infection or damage
What are the steps of the response after a barrier is breached?
- Stop bleeding (coagulation)
- Acute inflammation (leukocyte recruitment)
- Kill pathogens, neutralise toxins, limit pathogen spread
- Clear pathogens/ dead cells (phagocytosis)
- Proliferation of cells to repair damage
- Remove blood clot – remodel extracellular matrix
- Re-establish normal structure/ function of tissue
Define acute inflammation
Complete elimination of a pathogen followed by resolution of damage, disappearance of leukocytes and full regeneration of tissue
Define chronic inflammation
Persistent, un-resolved inflammation
What are the hallmarks of inflammation?
- Increased blood supply
- Increased vascular permeability
- Increased leukocyte trans-endothelial migration ‘extravasation’
What does C’ (complement) do?
- Lyse microbes directly (membrane attack complex)
- Increase chemotaxis
- Opsonisation (C3b – important to remember)
Describe the steps of phagocytosis
- Binding
- Engulfment
- Phagosome formation
- Lysosome fusion (phagolysosome)
- Membrane disruption
- Antigen presentation/ secretion
Why do we need adaptive immunity?
- Microbes evade innate immunity (proteases, decoy proteins, etc)
- Intracellular viruses and bacteria ‘hide’ from innate immunity
- Need memory to specific antigen – ‘seen it before so faster response’
- Cell Mediated - T cells - intracellular microbes
- Humoral (Ab) - B cells - extracellular microbes
What do major histocompatibility complexes do?
Display peptide from self OR non-self proteins (e.g. degraded microbial proteins) on the cell surface – invasion alert
Where is MHC I found?
glycoproteins on ALL nucleated cells
Where is MHC II found?
glycoproteins ONLY on APC
What is MHC III for?
code for secreted proteins (complement)
What type of antigen does MHC I form on?
Intrinsic Intracellular
(eg. virus)
What type of antigen does MHC II form on?
Extrinsic extracellular
(phagocytosis)
What type of T cell works at MHC I?
Cytotoxic Tc (CD8)
What type of T cell works at MHC II?
Helper Th (CD4)
What do Tc (CD8) cells do at MHC I?
Kill infected cell with intracellular pathogen
What do Th (CD4) cells do at MHC II?
HELP B cells make Ab to extracellular pathogen, can help directly kill
Which cells are involved in cell mediated immunity?
APCs
T cells
Which APCs are involves in cell mediated immunity?
Macrophages
Dendritic cells
B cells
What does cell mediated immunity require?
Requires intimate cell to cell contact to:
- Control Ab responses via contact with B cells
- Directly recognise and kill viral infected cells
What else cell mediated immunity require?
- Major histocompatibility complex (MHC)
- Intrinsic (endogenous) antigens
- Extrinsic (exogenous) antigens
- Recognise self or non-self
What do T cells only respond to?
DO NOT respond to soluble antigens only intracellular presented antigens
What is T cell selection?
T cells that recognise self are killed in the foetal thymus as they mature
What are the steps of B cell activation?
- B cells become activated upon binding with an antigen
- These then go to the lymph nodes where clonal expansion takes place with the cells differentiating into plasma cells
- These secrete Ab (usually IgM) which later turn into IgG
- B cells divide – CLONAL EXPANSION and differentiate into plasma cells and memory B cells
- Re-stimulation of memory B cells lead to secondary response
