Immune Response to Infection/Primary Immune Deficiencies Flashcards
What are the external epithelial route of entry for bacteria (3)
External surface
Wounds and abrasions
Insect bites
What are the mucousal surface routes of entry for pathogens (3)
Airways.
Gastrointestinal tract.
Reproductive treats.
What are the skin barriers to infection (3)
Tightly packed keratinised cells
Physiological factors
Sebacious glands
What are the skin physical barriers to infection (2)
Low pH
Low O2
What are the skin sebacious gland barriers to infection (3)
Hydrophobic oils repel water and microorganisms
Lysozomes destroy structural integrity of bacterial cell wall
Ammonia and defensins have anti-bacterial properties
What are the mucosal surface barriers to infection (2)
Secreted mucous
Cilia
How do secreted mucouses protect the mucosal surfaces from infection (4)
Physical barrier to trap invading pathogens.
Secretory IgA prevents bacterai and viruses attaching to and penetrating epithelial cells.
Lysozome and antimicrobial peptides directly kill invading pathogens
Lactoferrin acts to starve invading bacteria of iron
How do the cilia protect the mucosal surfaces from infection
Cilia directly trap pathogens and contribute to removal of mucous, assisted by physical manoeuvers such as sneezing and coughing
How do commensal bacteria protect us from pathogens (2)
Compete with pathogenic microorganisms for scarce resources
Produce fatty acids and bactericidins that inhibit the growth of many pathogens
What are the cells of the innate immune system (4)
Polymorphonuclear cells - neutrophils, eosinophils, basophils
Monocytes and macrophages
Natural killer cells
Dendritic cells
What are the soluble components of the innate immune system (3)
Complement
Acute phase proteins
Cytokines and chemokines
How do the cells of the innate immune system protect us from pathogens (5)
Essentially identical responses in all individuals
Cells express receptors that allow them to detect and home to sites of infection
Cells express genetically encoded receptors (pattern recognition receptors) that allow them to detect pathogens at site of infection
Cells have phagocytic capacity that allows them to engulf the pathogens
Cells secrete cytokines and chemokines to regulate immune response
How do polymorphonuclear cells react to/combat infection (7)
Migrate rapidly to site of injury
Express receptors for cytokines/chemokines - to detect inflammation
Express pattern recognition receptors – to detect pathogens
Express Fc receptors for Ig - to detect immune complexes
Capable of phagocytosis / oxidative & non-oxidative killing – particularly neutrophils
Release enzymes, histamine, lipid mediators of inflammation from granules
Secrete cytokines and chemokines to regulate inflammation
Where are polymorphonuclear cells produced
Bone marrow
What constitutes polymorphonuclear cells (4)
Neutrophils
Eosinophils
Basophils/Mast cells.
What are the mononuclear cells of he innate immune system (2)
Monocytes and macrophages
What happens to monocytes during an infective process
Monocytes are produced in the bone marrow, circulating in the blood.
They migrate to tissues where they differentiate to macrophages.
What are the macrophages of the liver
Kupffer cells
What are the macrophages of the kidneys
Mesangial cells
What are the macrophages of the bone
Osteoclas
What are the macrophages of the spleen
Sinusoidal lining cell
What are the macrophages of the lung
Alveolar macrophage
What are the macrophages of the CNS
Microglia
What are the macrophages of connective tissues
Histiocyte
What are the macrophages of the skin
Langerhan cells
What are the macrophages of the joints
Macrophage like synoviocytes
How do macrophages combat infection (7)
Present within tissue
Express receptors for cytokines and chemokines - to detect inflammation
Express pattern recognition receptors –to detect pathogens
Express Fc receptors for Ig - to detect immune complexes
Capable of phagocytosis / oxidative and non-oxidative killing
Secrete cytokines and chemokines to regulate inflammation
Capable of presenting processed antigen to T cells
How are phagocytes recruited to the area of injury
Cellular damage and bacterial products trigger the local production of inflammatory cytokines and chemokines
How do cytokines recruit phagocytic cells
Cytokines activate vascular endothelium enhancing permeability
How do chemokines attract phagocytic cells
Chemokines attract phagocytes (macrophages are already present in peripheral sites)
How are micro-organisms recognised during an immune response (2)
Pattern recognition receptors (e.g. toll-like receptors, mannose receptors) recognise generic motifts known as pathogen-assocaited molecular patterns (PAMPs) such as bacterial sugars, DNA, RNA
Fc receptors for Fc portion of immunoglobulin to allow recognition of immune complexes.
What role do opsonins play in endocytosis of pathogenic products
Opsonins act as a bridge between the pathogen and the phagocyte receptors
What roles do opsonins play in endocytosis (3)
Antibodies binding to Fc receptors.
Complement Complement binding to complement receptors
Acute phase proteins (eg. CRP)
How is a phalogysosome formed (2)
Phagosome and lysosome fuse to form phagolysosome
Protected compartment in which killing of the organism occurs
How are the organisms killed in the phagolysosome (2)
Oxidative killing
Non-Oxidative killing
What is involved in oxidative killing of organisms (3)
NADPH oxidase complex converts oxygen into reactive oxygen species - superoxide and hydrogen peroxide
Myeloperoxidase catalyses production of hydrochlorous acid from hydrogen peroxide and chloride
Hydrochlorous acid is a highly effective oxidant and anti-microbial
What is involved in non-oxidative killing of organisms (3)
Release of bacteriocidal enzymes such as lysozyme and lactoferrin into the phagolysosome
Enzymes present in granules
Each has a unique antimicrobial spectrum
Results in broad coverage against bacteria and fungi
What happens to the neutrophil after phagocytosis has occurred
Process of phagocytosis depletes neutrophil glycogen reserves and is followed by neutrophil cell death
What occurs when neutrophils die (3)
As the cells die, residual enzymes are released, causing liquefaction of closely adjacent tissue.
Accumulation of dead and dying neutrophils within infected tissue results in the formation of pus
Extensive localised formation of pus causes abscess formation
What products are involved in opsonisation (3)
Antibodies
Complement components
Acute phase proteins
Where are natural killer cells
Present within blood and may migrate to inflamed tissue
What do natural killer cells express (2)
Express inhibitory receptors for self-HLA molecules that prevent inappropriate activation by normal self
Express a range of activatory receptors including natural cytotoxicity receptors that recognise heparan sulphate proteoglycans
What do natural killer cells do (3)
Integrate signals from inhibitory and activatory receptors
Cytotoxic - kill ‘altered self’ as in malignant or virus infected cells
Secrete cytokines to regulate inflammation – promote dendritic cell function
Where are dendritic cells normally found
Peripheral tissues
What do dendritic cells express (3)
Express receptors for cytokines and chemokines - to detect inflammation
Express pathogen recognition receptors – to detect pathogens
Express Fc receptors for Ig - to detect immune complexes
Are dendritic cells capable of phagocytosis
Yes
What occurs after a dendritic call has phagocytosed (3)
Upregulate expression of HLA molecules
Express costimulatory molecules
Migrate via lymphatics to lymph nodes – mediated by CCR7
What do dendritic cells do in the lymph nodes
Present processed antigen to T cells in lymph nodes to prime the adaptive immune response
What immuno-regulatory functions do dendritic cells have
They express cytokines to regulate the immune response
How do antigens reach the lymph nodes
Via lymphatic system
How does the lymphatic system return to the blood
Via the thoracic duct
What are the components of the adaptive immune resoponse (3)
Humoural immunity (B lymphocytes and antibodies) Cellular immunity (T lymphocytes - CD4 and CD8 T cells) Soluble components (cytokines and chemokines)
What are the key characteristics of the adaptive immune system (4)
Wide repertoire of antigen receptors
Exquisite specificity
Clonal expansion
Immunological memory
What primary lymphoid organs are involved in lymphocyte development (2)
Bone marrow
Thymus
What is the role of the bone marrow in adaptive immunity (2)
Both T and B lymphocytes are derived from haematopoietic stem cells
Site of B cell maturation
What is the role of the thymus in the adaptive immune system (2)
Site of T cell maturation
Most active in the foetal and neonatal period, involutes after puberty
What secondary lymphoid organs are involved in lymphocyte development (3)
Anatomical sites of interaction between the naive lymphocytes and microorganisms
Spleen
Lymph nodes
Mucosal associated lymphoid tissue
What is the process of T cell maturation (3)
Arise from haematopoietic stem cells in bone marrow.
Exported as immature cells to the thymus where they undergo selection
Mature T lymphoctes enter the circulation and reside in the secondary lymphoid organs
What are the two pain subsets of T cells (2)
CD8+
CD4+
What HLA class do CD8+ T cells recognise
HLA class I
What HLA class do CD4+ T cells recognise
HLA class II
What is the ideal selectivity level for HLA molecules by T cells
Intermediate affinity
Approximately 10% of original cell produced
What is the role of CD4+ T cells (2)
Recognise peptides presented on HLA class II molecules Immunoregulatory functions via cell:cell interactions and expression of cytokines
What are the main CD4+ T cell subsets (5)
Th1 - help CD8 T cells and macrophages
Th17 - help neutrophil recruitment and enhance generation of autoantibodies
Treg - IL-10/TGF beta expressing. CD25+Foxp3+
TFh - follicular helper cells
Th2 - helper T cells
What are the roles of CD8+ T cells (5)
Sopecialised cytotoxic cells
Recognise peptides derived from intracellular proteins in associated with HLA class I
Kill cells directly (perforin and granzymes, express Fas ligand)
Secrete cytokines (IFNgamma, TNFalpha)
Particularly important in defence against viral infections and tumours.
What is meant by T cell memory
Response to successive exposures to antigen is qualitatively and quantitively different from that of first exposure - faster response
What do Th1 cells express/secrete (3)
Express CD4
Secrete IFNgamma and IL2
What do Treg cells express 92)
Foxp3
CD25
What is important that B cells do not do
Recognition of self - selected against this
What are the two responses that B cells have
Early IgM response
Later high affinity IgG, IgA, IgE secreting plasma cells and memory cells
How is the more specific B cell response conducted (3)
Dendritic cells prime CD4+ T cells.
CD4+ T cells help B cell differentiation - requires CD40L:CD40 interaction (occurs in lymphoid tissue).
B cell proliferation, somatic hypermutation and isotype switching to produce specific immunoglobulins
What are immunoglobulins
Soluble proteins made up of 2 heavy and 2 light chains
What does the heavy chain of the immunoglobulin determine
Antibody class (IgM, IgG, IgA, IgE, IgD)
What area is the antigen recognised by in the immunoglobulin
Antigen is recognised by the antigen binding regions (Fab) of both heavy and light chains
What determines the response to the antigen in the immunoglobulin
Constant region of the heavy chain (Fc)
What are the functions of antibodies (3)
Identification of pathogens and toxins
Interact with other components of the immune response to remove pathogens (Fc mediated)
Particularly important in defence against bacteria
How does the secondary B cell response differ from the primary B cell response (4)
The lag time between antigen exposure and the production of antibody is decreased (to 2-3 days)
The titre of antibodies produced is greatly increased
The response is dominated by IgG antibodies of high affinity
The response may be independent of help from CD4+ T lymphocytes
Where are pre-B cells found
In the bone marrow
What is IgA
Divalent antibody present within mucous which helps provide a constitutive barrier to infection
What is the germinal centre
Area within secondary lymphoid tissue where B cells proliferate and undergo affinity maturation and isotope switching
What is the complement system
> 20 tightly regulated, linked proteins
When triggered, enzymatically active other proteins in a biological cascade, resulting in a rapid, highly amplified response
Where are the compliment proteins produced
Liver
What are the three pathways of complement activation (3)
Classical (C1,2,4)
Alternative
MBL (C4,2)
What is the key shared step of all three complement pathways
C3
What is the final compliment pathway
C5-0
What is formed at the end of the compliment pathway
Membrane attack complex
What are the steps involved in the classical compliment pathway (4)
Formation of antibody-antigen immune complexes
Results in change in antibody shape – exposes binding site for C1
Binding of C1 to the binding site on antibody results in activation of the cascade
Dependent upon activation of acquired immune response (antibody)
What steps are involved in the MBL (mannose binding lectin) pathway of the complement system (3)
Activated by the direct binding of MBL to microbial cell surface carbohydrates
Directly stimulates the classical pathway, involving C4 and C2 but not C1
Not dependent on acquired immune response
What steps are involved in the alternative pathway of the compliment system (3)
Directly triggered by binding of C3 to bacterial cell wall components
eg lipopolysaccharide of gram negative bacteria, teichoic acid of gram positive bacteria
Not dependent on acquired immune response
Involves factors B, I and P
What does activation of C3 do in the compliment pathway (2)
It is the major amplification step in the complement cascade
It triggers the formation of the membrane attack complex via C5-9
What does the membrane attack complex do
Punches holes in bacterial membranes
What are the roles of the complement system (6)
Increases vascular pearmeability and cell trafficking to site of inflammation
Opsinisation of immune complexes keeps them soluble
opsonisation of pathogens to promote phagocytosis
Activates phagocytes
Promotes mast cell/basophil degranulation
Punches holes in bacterial membrane.
How is the complement system activated
Antibody binding to antigen
Binding to Fc receptors on macrophages and natural killer cells
What are cytokines (3)
Small protein messengers
Immunomodulatory function
Autocrine or paracrine dependent action
What are some examples of cytokines (6)
IL2, IL6, IL10, IL12, TNF-alpha, TGF-beta
What are chemokines (2)
Chemotactic cytokines - i.e. chemoattractants
Direct recruitment/homing of leukocytes in an inflammatory response
What are CCL19 and CCL21
Ligands for CCR7
Important in directing dendritic cell trafficking to lymph nodes
What are some other examples of chemokines (3)
RANTES
IL8
MIP1 alpha and beta
