Innate Immunity COPY Flashcards
What is the body’s first line of defence against pathogens ?
Innate Immunity
Is innate immunity specific ?
No
Is adaptive immunity ?
Yes
Describe the route of entry, mode of transmission, and pathogen for the following diseases:
- Influenza
- Meningococcal Meningitis
- Typhoid Fever
- Diarrhea
- Syphillis
INFLUENZA
- Route: Airway
- Transmission: Inhaled droplets
- Pathogen: Influenza virus
MENINGOCOCCAL MENINGITIS
- Route: Airway
- Transmission: Inhaled droplets
- Pathogen: Neisseria meningiditis
TYPHOID FEVER
- Route: GI tract
- Transmission: Contaminated food or water
- Pathogen: Salmonella typhi
DIARRHEA
- Route: GI tract
- Transmission: Contaminated food or water
- Pathogen: Rotavirus
SYPHILLIS
- Route: Genito-urinary
- Transmission: Physical contact
- Pathogen: Treponoma pallidum
How may pathogens gain access ?
Through mucosal surfaces
Through external epithelia
Identify examples of diseases which involve pathogen access to mucosal surfaces.
Influenza Meningococcal meningitis Typhoid fever Diarrhea Syphillis
Identify examples of diseases which involve pathogen access through external epithelia.
Athlete’s foot Anthrax Tetanus Yellow fever Malaria Lyme disease
Describe the route of entry, mode of transmission, and pathogen for the following diseases:
Athlete’s foot Anthrax Tetanus Yellow fever Malaria Lyme disease
ATHLETE’S FOOT
- Route: External surface
- Transmission: Physical contact
- Pathogen: Tinea Pedis
ANTHRAX
- Route: Wounds and abrasions
- Transmission: Minor skin abrasions
- Pathogen: Bacillus anthracis
TETANUS
- Route: Wounds and abrasions
- Transmission: Punctures
- Pathogen: Clostridium tetani
YELLOW FEVER
- Route: Insect bites
- Transmission: Moquito
- Pathogen: Flavivirus
MALARIA
- Route: Insect bites
- Transmission: Moquito
- Pathogen: Plasmodium
LYME DISEASE
- Route: Insect bites
- Transmission: Ticks
- Pathogen: Borrelia burgdorferi
What are the three phases of response to initial infection ? Identify the onset/duration of each
1) Innate Immunity (0-4 hours)
2) Early induced response (4-96 hours)
3) Adaptive Immune Response (>96 hours)
What are the main steps in innate immunity (step 1 of response to initial infection) ?
Infection –> Recognition by preformed, nonspecific effectors –> Removal of infectious agent
What are the main steps in early induced response (step 2 of response to initial infection) ?
Infection –> Recruitment of effector cells –> Recognition and activation of effector cells –> Removal of infectious agent
What are the main steps in adaptive immune response (step 2 of response to initial infection) ?
Infection –> Transport of antigen to lymphoid organs –>
Recognition by naive B and T cells –> Clonal expansion of effector cells –> Removal of infectious agent
What are the main types of barriers to infection ?
Mechanical, chemical, microbiological
Give examples of mechanical barriers to infection.
- Tight junctions between cells prevents access
- Air and fluid flow across epithelium
- Movement of mucus by cilia
Give examples of chemical barriers to infection.
- Fatty acids on skin
- Enzymes: lysozyme in saliva, sweat and tears.
- Low pH in stomach
- Antibacterial peptides: defensins (skin and gut) cryptidins (gut)
Give examples of microbiological barriers to infection.
-Normal flora compete for nutrients and attachment (biofilms), and also produce antibacterial substances (colicins)
What happens once a microorganism has gone across an epithelial barrier ?
Recognised and ingested by mononuclear phagocytes, or macrophages.
What are examples of receptors on phagocytes which aid recognition of microorganisms ?
Mannose receptor Glucan receptor Scavenger receptor CD14 CD11b/CD18
What are some of the bactericidal effects and agents produced by phagocytes ?
- Acidification: pH 3-4, bactericidal
- Toxic oxygen derived products: superoxide, hydrogen peroxide, hydroxyl radical
- Toxic nitrogen oxides: Nitric Oxide
- Peptides: defensins and other cationic proteins
- Enzymes:Lysosyme, acidhydrolases
- Competitors: Lactoferrin, vitamin B12 binding protein
What is the progenitor cell of all cellular elements of blood, rbc, platelets, white cells (including macrophages, T cells etc.) ?
Hematopoietic stem cell
What is a monocyte ? What is the difference between a monocyte and a macrophage ?
Monocytes: one of the three types of phagocytic cell of the immune system.
Circulate in bloodstream, differentiate into macrophages in tissue.
What is another name for granulocytes ?
Polymorphonuclear (PMN) leucocytes
What are the main types of granulocytes ?
Neutrophils, Eosinophils, Basophils
What are the main types of WBCs ?
Lymphocytes
Granulocytes (Neutrophils, Eosinophils, Basophils)
Monocytes (–> Macrophages)
What are the main phagocytic cells of the immune system ?
Neutrophils, Monocytes, Dendritic Cells
What is the most important/numerous cell of innate immunity ?
Neutrophils
What is the main function of eosinophils ?
Parasite defence
What is the most common granulocyte/Polymorphonuclear leukocyte ?
Neutrophils (99% of all PMNs)
What proportion of all leucocytes do neutrophils make up ?
70%
How long do neutrophils survive in circulation, and in tissue ?
In circulation, around 12 hours, once in tissue survive for maybe only 2 days.
How many rounds of phagocytosis can neutrophils usually undertake ?
Just one
What are the main features of Chronic granulomatous disease ?
Failure in respiratory burst
Superoxide production limited
Sntibacterial activity impaired
Why and how may neutrophils adapt ?
To prevent growth of parasites that can live in phagocytic cells.
How is the short life span of neutrophils beneficial ?
Since antimicrobial products damage host tissues, short lifespan may limit host damage
What are the consequences of Alpha 1-antitrypsin deficiency ?
Elastase from neutrophils not adequately inhibited, excessive tissue damage during inflammation (e.g. in pulmonary emphysema)
What are the contents of the eosinophil granules ?
Histamine, peroxidase, RNase, DNases, lipase, plasminogen, Major Basic Protein
How long do eosinophils survive in circulation, and in tissue ?
Circulate for 12 hours, survive in tissues for 3 days
What is eosinophilia ? When might it occur ?
Increase in number of eosinophils, more than 500 per microlitre blood
May occur in parasitic infections of gut, some vascular diseases, Hodgkin’s Disease, Addison’s Disease
What is eosinopenia ? When may it occur ?
Decrease in number of eosinophils
When glucocorticoids are used
Describe the main features of Eosinophilia-myalgia syndrome (EMS).
Possibly fatal neurological condition
Eosinophils increased in blood
Potential interference with histamine metabolism
What is the function of basophils ?
Similar and complementary to eosinophils and mast cells.
What is the function of mast cells ?
When activated release a number of substances that effect vascular systems (e.g. due to IgE mediated triggering in allergies)
Which is the least common Polymorphonuclear leukocyte ?
Basophils
What are some of the substances secreted by basophils upon activation ?
Histamine
Proteoglycans
Leucotrienes
Some cytokines including IL-4 (potentially important for IgE and allergy)
What are the types of lymphocytes ?
Beta or T lymphocytes
What is the function of each of beta and T lymphocytes ?
B-cells produce antibody
T-cells becoming cytotoxic T cells (CD8) or helper T cells (CD4)
What is the most important cell of the adaptive immune response ?
Lymphocytes
What are plasma cells ? What is their role ?
Activated beta-cells
Makes large amounts of a specific antibody.
Which kind of leukocyte are Natural Killer Cells ? What is their role ?
Large granular lymphocytes
Recognise virally infected cells non- specifically
What is the main role of dendritic cells ?
Bridges innate and adaptive immune responses
Specialised in antigen uptake and antigen presentation
What responses do viral-infected cells produce ?
Produce alpha and beta interferons which:
- Induce resistance to viral replication in all cells
- Increase MHC class 1 expression and antigen presentation in all cells
- Activate NK cells to kill virus-infected cells
What is the key difference between NK cells and CD8 cells ?
- NK cells are not antigen specific
- NK cells do not require to undergo the lengthy clonal expansion of T cells in lymph nodes when virus is detected (hence quicker response)
How quick is the NK response to viral infection ?
Quick (starts around day 2)
How do NK cells know whether or not to kill a cell ?
Through interaction of its own surface activator receptor and inhibitory receptor with molecules on the surface of cells.
Inhibitory receptor of NK cell binds to MHC 1 protein so if MHC 1 present, negative signal predominates and killing does not take place (in healthy cell, still get positive signal because activating receptor of NK cell still interacts with a protein on healthy cell but negative signal predominates).
In a virus infected cell, MHC 1 expression is downregulated so inhibitory receptor has nothing to bind with whereas activating receptor does. i.e. positive signal predominates and NK cell kills virus infected cell.
What kind of molecule if a complement ? What is its function ?
Heat labile component of plasma that act in concert with
antibodies to kill some bacteria
What are the activation pathways which exist that trigger the complement cascade ?
- Classical Pathway: Antibody binds to specific antigen on pathogen surface
- Lectin Pathway: Mannose-binding protein binds to pathogen surface
- Alternative Pathway: Pathogen surface creates local environment conducive to complement activation
What is the consequence of the complement activation (as a result of the classical, lectin, and alternative pathways) ?
- Recruitment of inflammatory cells
- Opsonisation of pathogens (facilitates uptake and killing by phagocytic cells)
- Lysis and death of pathogens
What is the function of C3b, C3a, C5a ?
C3b: opsonin
C3a: Peptide mediator of inflammation
C5a: Peptide mediator of inflammation
What is the start and end point of the complement cascade ? How does it get from one to the other ?
C1 through C9 (cleavage of one into two again and again)
How is the classical pathway initiated ?
By activation of C1 complex
How is the lectin pathway initiated ?
By activation of a complex made of MBL MASP-1 and MASP2.
How is the alternative pathway initiated ?
By spontaneous hydrolysis of serum C3
What are some factors which increase phagocytosis ?
Antibody binding + Opsonisation
What is the membrane attack complex (MAC) ?
Using complements C5 through C9, membrane attack complex forms.
This punches pores in surface of bacteria
Contents leak out
Lysis takes place
How is the complement cascade system regulated ?
Through regulatory proteins such as:
- Factor H (makes complement more susceptible to cleavage and inactivation by Factor I)
- C1 inhibitor (dislodges interaction between C1r and C1s, and active C1 complex in the classical pathway)
- CD59 = protectin (present in most cells in the body, to prevent final assembly of MCP in normal body cels)
What are possible causes of neutropenia ?
Genetic or due to medication including chemotherapy
