immunity Flashcards
innate defences
surface barriers:
* Skin
* Mucous membranes
Internal defences:
* Phagocytes
* Natural killer cells
* Inflammation
* Antimicrobial proteins
* Fever
adaptive defences
humoral immunity - B cells
cell mediated immunity - T cells
naturally acquired immunity
1.active
- passive
- pathogen enters body naturally, innate and adaptive defences respond and provide long term defences
- antibodies passed from mother to foetus via placenta, breast milk to provide immediate short term defences
Artificially acquired immunity
1.active
- passive
- antigen enters through vaccination, innate and adaptive defences respond and provide long term defences
- antibodies from immune individuals injected to provide short term Protection.
what are the polymorphonuclear leukocytes
- neutrophils
- eosinophils
- basophils
what are the antigen presenting cells
- dendritic cells - skin + tissues
- monocytes - precursor to tissue macrophage
- macrophages - tissues
- ( B cells - adaptive)
what are neutrophils
- most abundant phagocytes
- first line of defence
- granules containing cytotoxic molecules, antimicrobial enzymes are released
how do neutrophils digest
eosinophils funtion
- type of leukocytes that is produced in people with parasitic infections
- activate mast cells to release histamine
basophils function
- release anticoagulant heparin into blood to prevent blood coagulation
- bind to IgE to protect against allergens
- resident to GI tract
- has heparin and histamine in granules
mast cells function
- release histamine - causes dilation of small blood vessels, increases vascular permeability and contracts smooth muscle
- Develop rapid hypersensitivity reactions including production of IgE antibodies in response to an antigen, binding of IgE to Fc receptors of mast cells, cross-linking of the bound IgE by the antigen and release of mast cell mediators
- heparin and histamine in granules
monocytes function
-Make up 2-10% of white blood cells
-Immature in blood (1-2 days)
-Produced in bone marrow, travel to tissues, mature, enlarge and become tissue macrophages
-Roles inphagocytosis,antigen presentationand cytokine production
-Much more powerful phagocytes than neutrophils
-Can phagocytise as many as 100 bacteria
-Can engulf large particles such as malarial parasites
-Can survive after phagocytosis for months
-kidney shaped nucleus
Macrophages function
-Effector cells of innate immune system found essentially in all tissues
-Develop from monocytes and are most robust phagocytic cells
-Performantigen presentationand canactivate memory cells
-Free macrophages wander through tissue spaces, for example alveolar macrophages
-Fixed macrophages are permanent residents of some organs such as microglia (brain)
-Source of IL-1
natural killer cells
-non phagocytic, large granular cytotoxic lymphocytes
-kill cells by inducing apoptosis in cancer cells and virus infected cells
necrosis vs apoptosis
necrosis - is accidental cell death occurring due to uncontrolled external factors causing inflammation
Apoptosis - is programmed cell death where the cell actively kills itslef
function of antigen presenting cells
-is an innate immune cell that detects antigens and activates the adaptive immune response
what are dendritic cells
-Main antigen-presenting cells(APCs) of the immune system
-Role in activatingT helper cellsandmemory cells
function of MHC (major histocompatibility complex) class 1 and 2
-they help APC to present cells
when do immature dendritic cells mature
once they are in the presence of inflammation the cytokines stimulate them and become mature and migrate to lymph nodes
how do dendritic cells contribute to the development of HIV
They bind to HIV and transfer it to the lymph node where it contributes to the development of the infection by transferring the virus to CD4 T helper cells
what are cytokines
Small proteins – secreted by cells of the immune system
Signalling molecules released by neutrophils, macrophages, TLRs, NK cells and lymphocytes
Affect the behaviour of other cells
what are interferons
Interferons are cytokines which are produced in response to viral infection
Protein kinase R (PKR) pathway is triggered by dsRNA and interferon
Produce an ‘anti-viral state’ in target cells
Acts on cell that produces it, as well as neighboring cells
Shuts down protein synthesis machinery of cells, thus preventing viral replication
Steps for phagocyte mobilisation
- Leukocytosis: release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
- Margination: endothelial cells of capillaries in inflamed area project cell adhesion molecules (CAMs) into vessel lumen that attach to passing neutrophils, causing them to slow and roll along, clinging to vessel wall
- Diapedesis: neutrophils flatten and squeeze between endothelial cells, through capillary walls, moving into interstitial spaces
- Chemotaxis: inflammatory chemicals act as chemotactic agents that promote positive chemotaxis of neutrophils toward injured area
- As attack continues, monocytes arrive later 12 hours after leaving bloodstream, they are transformed into macrophages
These “late-arrivers” replace dying neutrophils and remain for cleanup prior to repair
what is the complement system
-series of over 30 proteins
-when foreign material is detected it initiates a
cascade of reactions that amplify the signal
-cooperates with other host defences to generate inflammation and remove the pathogen
-contains proteins C1-9 factors B,D,H and I
main functions of complement system
-facilitates phagocytosis
Generates activated complement proteins opsonisingantigens (marking antigens for phagocytosis by attaching to the surface/coating a particle with opsonins allowing interactions with receptors on phagocytes)
-lysis of pathogens
lyses bacterial cell wall
-inflammation
Attracts moremacrophagesandneutrophils
What are toll like receptors
Phagocytes such as dendritic cells identify pathogens by recognising pathogen-associated molecular patterns (PAMPs) using pathogen recognition receptors (PRRs) - toll like receptors are an example of PRRs.
Toll-like receptors (TLRs) link microbial products (PAMPs) to transcription factor activation in a signaling pathway
What is an epitope
The region of an antigen that interacts with an antibody
Where is the Fc and Fab region
IgM immunoglobulins characteristics
- have a pentameric structure
- produced first during primary response
- 3rd most abundant
- marker of recent infection
- activates complement has 5 complement bonding sites
- too big to cross placenta
IgG immunoglobulins characteristics
- most prevalent antibody in serum 70%
- crosses placenta from mother to foetus, protects newborn until can produce own antibodies
- activates complement
- secreted high quantities in secondary response (faster, more effective)
IgA immunoglobulin characteristics
- 2nd most common
- most prevalent in secretions such as tears, saliva and mucous
- monomeric in serum but dimeric with secretory component in lumen of GI and respiratory tract
- resistant to digestion and can activate complement system
- found in breast milk
- localised protection on mucous membranes
IgE immunoglobulin characteristics
- monomeric structure
- triggers allergic responses, binds to basophils in blood and mast cells in tissues and release histamine which causes inflammation
- associated with anaphylaxis
- higher in people with asthma, hay fever and allergic disorders
- least abundant
- mediates type 1 hypersensitivity reactions
Affinity is the…
strength of the interaction between an epitope and antibody-antigen binding site or it is the association constant for binding (KA) KA= K1/K2
Consequences of antigen-antibody binding
Neutralisation
Agglutination
Precipitation of soluble antigens
Complement fixation
How does lysozyme disrupt peptidoglycan
Cleaves bond between the alternating sugars that make up peptidoglycan
Most effective against gram positive bacteria
Actions of collectins, ficolins and pentraxins
- Soluble pattern recognition
receptors - Act as opsonins that bind to
pathogens and infected cells
targeting them for phagocytosis - Activate complement through the
classical pathway/lectin pathway
Which proteins make up the classical pathway
C1-C9
C1 structure
Has c1s, c1r, c1q
Each c1q can bind to fc region of antibodies so each c1 can bind up to 6 antibodies
C1r and c1s are both serine proteases which are hidden
They are wrapped in calcium so if lack of calcium lack of c1
When c1q receptors bind to antibodies that are bound to antigens…
The c1 molecule twists exposes the c1r and c1s this activates c1 molecule which cleaves c4 into c4a and c4b and c2 into c2a and c2b
C4b and c2b bind together on the surface of the pathogen forming c4bc2b=c3 convertase
C3 convertase cleaves c3 into c3b and c3a
How do T-cells recognise self vs non- self
For mature T cell to develop without being self-reactive, it must go through both positive and negative selection
A) T cell binds to antigen-MHC complex from infected cell causing cell death
B) Positive selection: T cell in thymus that binds moderately to MHC complex and survives
C) Negative selection: T cell that binds too strongly to MHC will likely be self-reactive and result in death
Factor B binds to…
C3b and antigen membrane and is cleaved by factor D to form Ba and Bb
Leaving c3bBb on the antigen membrane
What is the amplification step in the alternative pathway
c3bBb acts as c3 convertase and after this point it will follow the classical pathway
How is the alternative pathway regulated
C1 inhibitor Dissociates factor c3b form Bb which shuts down the alternative c3 convertase
Factor H a cofactor for factor I which inactives c3b into ic3b
ic3b is still a potent opsonin which cant propogate the alternative pathway
Complement deficiency conditions
