Innate and Adaptive Immunity Flashcards
When are the bodies basic defences active?
At all times
What are the kind of basic defences of the body?
- Mechanical
- Chemical
- Microbiological
Where are the main points of defence in the body?
- Skin
- Gut
- Lungs
- Eyes/nose
What are the mechanical defences of the body?
- Epithelial cells joined by tight junctions at the skin, gut, lungs and eyes/nose
- Longitudinal flow of air or fluid in the skin and gut
- Movement of mucus by cells in the lungs
- Tears and nasal cilia in the eyes/nose
What are the chemical defences of the body?
- Fatty acids in skin
- Low pH and enzymes (including pepsin) in the gut
- Enzymes (lysozymes) in tears
- Antibacterial peptides in the skin, gut, and lungs
What are the microbiological defences of the body?
Normal flora in the skin and gut
What are the three most important basic defences in the body?
- Epithelia
- Antibacterial peptides
- Enzymes
What is innate immunity?
The body’s first line of immune protection to infection after physical barriers such as the skin have been broken
What are the characteristics of innate immunity?
- Rapid
- Pre-existing
- Lacks specificity and memory
What does innate immunity act in response to?
Pathogen Associated Molecular Patterns (PAMPs)
Is adaptive immunity fixed?
No, it adapts to different challenges it faces
What are the characteristics of adaptive immunity?
- Slow
- Specific
- Has memory
- Increases in intensity with subsequent exposure
What are the types of immunity?
- Cellular
- Humoral
What cells are involved in innate cellular immunity?
- Neutrophils (or polymorphs)
- Macrophages
What are macrophages called when in the blood?
Monocytes
What do the cells of the innate cellular immune response do?
Phagocytose microbes in order to destroy them via intracellular killing
What is involved in innate humoral immunity?
- Complement system
- Cytokines
What does the complement system involve?
A cascade of serum proteins
What happens in the process of phagocytosis?
- Initially, the cells migrate to the area via a chemotactic gradient of molecules
- Phagocytes recognise their targets by binding to their PAMPs
- The pathogen is then internalised via phagocytosis, and the phagosomes is fused with a lysosome, where the killing of microbes takes place
What molecules from the chemotactic gradient that causes phagocytes to migrate to the required area?
- C5a
- Leukotrienes
- IL-8
What releases the chemotactic molecules that cause phagocytes to migrate to the required area?
Damaged cells, or the dendritic cells of the area
How is recognition of targets by phagocytes enhanced?
If the microbe has been opsonised
How are microbes opsonised?
Via IgG or C3b
Why is target recognition by phagocytes enhanced when the microbe has been opsonised?
As phagocytes have Fc and C3b receptors
How does the killing of microbes by phagocytes take place?
Using oxygen dependant or oxygen independant processes
What are the oxygen dependant processes of microbial killing?
Producing ROS via NAPH oxidase
What are the oxygen independant processes of microbial killing?
Lysosomal enzymes
How do the innate immune cells recognise various classes of microbe?
By Pathogen-Associated-Molecular-Patterns (PAMPs)
What are PAMPs?
Structures that groups of pathogens share
What are receptors that recognise PAMPs known as?
Pattern Recognition Receptors (PRRs)
Give two examples of PRRs
- Toll-like receptors
- Mannose receptors
Give 6 examples of Toll-Like Receptors (TLRs)
- TLR2
- TLR3
- TLR4
- TLR5
- TLR7
- TLR8
What is the PAMP for TLR2?
Peptioglycan
What is the PAMP group for TLR2?
Gram positive bacteria
What is the PAMP for TLR3?
dsRNA
What is the PAMP group for TLR3?
Viruses
What is the PAMP for TLR4?
LPS
What is the PAMP group for TLR4?
Gram negative bacteria
What is the PAMP for TLR5?
Flagellin
What is the PAMP group for TLR5?
Bacteria
What is the PAMP for TLR7?
ssDNA
What is the PAMP group for TLR7?
Viruses
What is the PAMP for TLR9?
dsDNA
What is the PAMP group for TLR9?
Viruses
What happens after the PRRs have responded to the PAMPs?
They will then go on to stimulate further innate and adaptive immune responses
What is the clinical significance of TLR-4?
It is responsible for septic shock seen in septicaemia of Gram negative bacteria
What is the complement system made up of?
A large number of different plasma proteins that interact with one another
What do the plasma proteins in the complement system interact with each other to do?
- Opsonise pathogens
- Induce a series of inflammatory responses that help to fight infection
What does the interaction of plasma proteins in the complement system cumulate in?
The Membrane Attack Complex (MAC)
What is a crucial feature of the complement system?
Several complement proteins are proteases that become activated only after cleavage
What is the result of the complement system being a proteolytic cleavage cascade?
There is an amplification effect that produces a large number of the effector molecules
How many pathways of complement activation are there?
3
What do the pathways of complement activation result in?
The formation of C3 convertase
What does C3 covertase do?
Activates the rest of the complement pathway
What are the pathways of complement activation?
- Classical pathway
- Lectin pathway
- Alternate pathway
What happens in the classical pathway of complement activation?
- IgM or IgG antibodies bind to antigens on microbial cellular surfaces, to form antigen-antibody complexes
- C1 binds to 2 of their Fc regions Cleavage of C2 and C4
- C3 convertase formed
What happens in the lectin pathway of complement activation?
- Plasma mannose binds to lectin on microbes
- Cleave of C2 and C4
- C3 convertase formed
What happens in the alternate pathway of complement activation?
- Small amount of C3b in serum deposits on the microbe surface
- Microbe bound C3b binds to another protein to form C3 convertase
What happens to C3 convertase once formed?
It is covalently bonded to the pathogen surface Here, they cleave C3 to generate large amounts of C3b and C3a
What is C3a?
A peptide mediator of inflammation
What is C3b?
The main effector molecule of the complement system
What does C3b do?
- Acts as an opsonin, targeting the pathogen for destruction by phagocytes with C3b receptors
- Removal of immune complexes
- Binds to C3 convertase to form C5 convertase
What does C5 convertase do?
Produces C5a and C5b
What is C5a?
A potent inflammatory peptide
What does C5b do?
Leads to formation of the membrane attack complex (MAC)
What are the terminal complement components?
C5b, C6, C7, C8, C9
What do the terminal complement components do?
- Form MAC
- Lysis of certain pathogens and cells
What is required for production of the terminal complement components?
C3b
What complement components are involved in phagocyte recruitment?
C3a, C5a
What cells are involved in adaptive cellular immunity?
- B cells
- T cells
What are the types of B cells?
- Plasma
- Memory
What cells are involved in adaptive humoral immunity?
Antibodies
What does adaptive immunity utilise?
The antigen recognition arm of the immune system
What does adaptive immunity have to be able to do to utilise the antigen recognition arm of the immune response?
Distinguish self from non-self by means of specialised receptors
When can the immune system be particularly damaging?
If cells have specificity for self (autoimmunity)
Why is it important that adaptive immunity has memory of previously encountered infections?
It gives an accelerated and increased response on subsequent encounters
What is the accelerated and increased response on subsequent encounters due to the memory of adaptive immunity known as?
The secondary response
What does adaptive immunity show for individual pathogens?
A very high degree of specificity
What is the high degree of specificity of adaptive immunity to individual pathogens determined by?
The antigen-specific receptors that are expressed by individual clones of T and B lymphocytes
What is the problem with the rapid immunological response to a second encounter with measles virus?
It is of no value if cells and antibodies are rapidly mobilised, but have the wrong specificity
What is the primary exposure?
When an antibody is encountered for the first time
What is the lag phase?
The period of time before any antibody that has been encounter for the first time is detectable
What has to happen during the lag phase?
The antigen has to be recognised, processed, and presented by APC’s to lymphocytes
What do the events happening in the lag phase cumulate it?
The appearance of the primary antibody response
What is the antibody of primary response?
IgM
What happens after a while following the primary antibody response?
The serum concentration of IgM falls
What happens if an antibody that a patient has previously been exposed to is administered again?
There is a rapid appearance of antibody with very little lag phase
What is the second exposure to the same antibody called?
The secondary antibody response
What is the antibody of secondary response?
IgG (usually)
What is the secondary response due to?
The presence of memory cells
What type of immunity is memory a function of?
Adaptive. It is not seen in innate immunity
What is acute inflammation?
The response of living tissue to injury
What is acute inflammation initiated to do?
Limit the tissue damage
What is chronic inflammation?
Chronic response to injury with associated fibrosis
What are the cardinal signs of inflammation?
- Heat
- Erythema (redness)
- Oedema (swelling)
- Pain
- Loss of function
What are the 5 steps of acute inflammation?
- Vasodilation
- Gaps form in endothelium
- Exudation
- Margination and Emigration
- Macrophages and lymphocytes migrate
What happens in the vasodilation stage of acute inflammation?
Small adjacent blood vessels dilate with increased blood flow
What happens in the gap formation stage of acute inflammation?
Endothelial cells swell and retract, so there is no longer a completed intact internal lining
What happens in the exudation stage of acute inflammation?
Vessels become leaky, and water, salts, and small plasma proteins leak through as exudate
What happens in the margination and emigration stage of acute inflammation?
- Circulating neutrophils adhere to swollen endothelial cells in margination.
- Neutrophils then migrate through the vessel basement membrane in emigration
How do macrophages and lymphocytes migrate?
In a similar way to neutrophils
What are inflammatory cells attracted by?
Chemokines, such as leukotrienes, IL-8 and C5a
How are cells involved in the immune response controlled and communicate?
Via cytokines
What makes cytokines?
White blood cells
What are cytokines commonly called?
Interleukins
Give 3 pro-inflammatory cytokines
- IL-1
- IL-6
- TNF
What are the chemical mediators for vasodilation?
- Histamine
- Prostaglandins
- C3a
- C5a
What are the chemical mediators for increased vascular permeability?
- Histamine
- Prostaglandins
- Kinins
What are the chemical mediators for emigration of leukocytes?
- Leukotrienes
- IL-8
- C5a
What is meant by active immunisation?
Stimulating the patient’s own immune system with an appropriate antigen
How can active immunisation be bought about?
Injecting an attenuated form of the live organism response for the disease in question, killed organisms, or a denatured toxin (toxoid)
What happens in active immunisation?
There is a lag phase, followed by the appearance of antigen-specific immune cells and antibodies. Immunological memory is formed
What must be true of a patient receiving active immunisation?
They must have an intact immune system
What can happen if an immunocompromised patient is inoculated with a live vaccine?
It can be fatal
What is meant by passive immunisation?
Administration of a serum containing antibodies against as a disease or toxin
What is the advantage of passive immunisation?
- It is quick, with no lag phase
- Doesn’t require intact immune system
What is the disadvantage of passive immunisation?
- No immunological memory formed
- Immune protection short lived
What are malignancies of the immune system characterised by?
The proliferation and accumulation of malignant leukocytes blocked at different stages of development
What happens in leukaemia?
There are increased number of white blood cells, which may dominate the peripheral blood picture
When do lymphomas arise?
When the malignant cells are found within tissues, rather than blood e.g. lymph nodes, spleen
What types of leukocytes can malignancies occur for?
Any
What does malignancy of the immune system give rise to?
A dominant, non-functional population of immune cells
What are malignancies of the immune system associated with?
Secondary immune deficiencies
What are the origin cells of the immune system?
Pluripotent, haematopoietic stem cells in the bone marrow
What are the stages of production of immune cells?
Proliferation and differentiation of haemopoietic stem cells
What happens in proliferation of haemopoietic stem cells?
Starting with a stem cell, the cell divides into two. One replaces the original stem cell, and one that differentiates
What is the process of the stem cell proliferating to provide one cell that replaces the original called?
Self-renewal
What happens in differentiation of haemopoietic stem cells?
Haemopoietic progenitor will first differentiate to form either a myeloid blast or a lymphoid blast
What forms from myeloid blast cells?
Either RBC, WBC or platelets
What forms from lymphoid blast cells?
Immunoresponse cells
What does the haemopoietic progenitor differentiate under the influence of?
A particular cytokine
What causes differentiation to RBCs?
Erythropoietin
What causes differentiation to platelets?
Thrombopoietin
What is erythropoiesis controlled by?
Partial pressure of oxygen
What does a low pO2 do?
Stimulates increased erythropoietin
What cells are produced from the pluripotent haemopoietic stem cell in the bone marrow?
- Common lymphoid progenitor
- Common myeloid progenitor
- Erythrocyte
What is produced from the common lymphoid progenitor?
- B cell
- T cell
- NK cell
- Immature dendritic cell
What is the effector cell from a B cell?
Plasma cell
What is the effector cell from a T cell?
Activated T cell
What is the effector cell from a NK cell?
Activated NK cell
What route to B cells, T cells and NK cells take after production in the bone marrow?
They go into the blood, and then travel to lymph nodes
What happens to immature dendritic cells once produced in the bone marrow?
They pass into the blood, and then the tissues, and then become mature dendritic cells in the lymph nodes
What is produced from the common myeloid precursor?
- Granulocyte/macrophage progenitor
- Megakaryocyte/erythrocyte progenitor
What is produce from the granulocyte/macrophage progenitor?
Granulocytes (or polymorphonuclear leukocytes)
Where are granulocytes produced from granulocyte progenitors?
In the blood
What cells are considered to be granulocytes?
- Neutrophils
- Eosinophils
- Basophils
- Unknown precursor of mast cells
- Monocytes
Where do unknown precursors of mast cells become mast cells?
In the tissues
What do monocytes become?
Macrophages
Where do monocytes become macrophages?
In tissues
Where does the megakaryocyte progenitor produce megakaryocytes?
In the bone marrow
What do megakaryocytes become?
Platelets
Where do megakaryocytes become platelets?
In the blood
What do erythroblasts become?
Erythrocytes
How to lymphocytes appear microscopically?
Small cells with deeply basophilic nucleus and little cytoplasm
What happens to lymphocytes when exposed to antigen?
They become larger, chromatin is less dense, and cytoplasm volume increases. It is then known as a lymphoblast
What is the purpose of lympocytes?
- Production of antibodies (B lymphocytes)
- Cytotoxic and helper functions (T cells)
What do B cells give rise to?
Plasma cells
What do plasma cells do?
Produce antibodies
Where are plasma cells found?
In spleen and lymph nodes
Rarely seen in blood
Where do T cells undergo maturation?
In the thymus
What are the types of T cells?
- CD4+ helper
- CD8+ cytotoxic
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What do CD4+ helper cells do?
Secrete cytokines that act on other cells
What do CD8+ cytotoxic cells do?
Cause lysis of infected cells
How big are monocytes?
16-20µm in diameter
Largest nucleated cell of blood
What shape of the monocyte nucleus?
Kidney shaped
What happens when a monocyte migrates into tissues?
It develops into a macrophage
What is the main role of the macrophage?
It is the principle resident phagocyte of the tissues
What does the macrophage have?
Receptors for antibodies and complement
What kind of macrophages are found in the CNS?
Microglia
What kind of macrophages are found in the liver?
Kupffer cells
What kind of macrophages are found in the lungs?
Alveolar macrophages
What kind of macrophages are found in the bone?
Osteoclasts
What are dendritic cells?
Progessional antigen presenting cells
What is the apperance of dendritic cells characterised by?
Long, finger-like processes
What do dendritic cells do?
Take up particulate matter by phagocytosis, and large amounts of extracellular fluid and it’s contents by macropinocytosis
What is the most common type of leucocyte?
Neutrophils
What kind of nucleus do neutrophils have?
Multi-lobed
What kind of cells are neutrophils?
Short-lived phagocytic cells
What do neutrophils have in their cytoplasm?
Granules contaning numerous bactericidal substances
What do neutrophils do?
Avidly phagocytoses particles that are opsonised by IgG or complement
Function as an effector cell of humoral immunity
What kind of nucleus do eosionphils have?
Bi-lobed
What do eosinophils have in their cytoplasm?
Granules contain highly basic or ‘cationic’ proteins
What are eosinophil granules important for?
Killing larger parasites, including worms
What kind of nucleus do basophils have?
Bi- or tri-lobed nucleus
What do basophils have in their cytoplasm?
Granules containing heparin, histamine and other vasoactive amines
What do basophils have on their cell surface?
High affinity receptors for IgE
When are basophil granules released?
At sites of inflammation/hypersensitivity
What kind of nucleus do mast cells have?
Circular
What kind of cell are mast cells?
Tissue cell
Not bone marrow derived
What are mast cells similar to?
Basophils, in that they have granules of histamine
What kind of cell is this?
Lymphocyte
What kind of cell is this?
Plasma cell
What kind of cell is this?
Monocyte
What kind of cell is this?
Macrophage
What kind of cell is this?
Dendritic cell
What kind of cell is this?
Neutrophil
What kind of cell is this?
Eosionphil
What kind of cell is this?
Basophil
What kind of cell is this?
Mast cell
