W7 Immunology of Infectious diseases Flashcards
What is the primary function of the immune system?
What are the host defences against infections? (2)
‘Defend against and eliminate ‘foreign’
material and minimise any damage that may be caused’
- Innate immune responses
-nonspecific response not intrinsically affected by prior contact with infectious agent - Adaptive immune responses (Acquired)
* Response involves highly specific recognition and immunological memory ie. Response involves altered reactivity to a specific antigen such that a more rapid response against the antigen occurs with subsequent exposure
-Humoral immunity involving antibodies
-Cell-mediated immunity involving T-cells
* Adaptive immune responses amplify protective mechanisms of innate immunity and directs or focuses such innate mechanisms to sites of antigen entry
What are the different cells in the immune system?
Leukocytes:
Lymphocytes-
T cells= Secrete chemical messengers
B cells/Plasma cells- Secretes antibodies
NK cells- Destroy virally infected cells
Accessory cells
* Monocytes/macrophages
* Neutrophils
* Eosinophils
* Basophils
* Mast cells- release histamine
- T cells directly destroy pathogens, but they regulate nearly all other types of the adaptive immune
- Accessory cells activate lymphocytes, carry out phagocytosis, and secrete powerful effector molecules
-Key phagocytic cells: Neutrophils and macrophages
What is the Innate Immune Response?
- Innate defence against entry of micro organisms:
-Commensal microorganisms
-Physical barrier
-Secretions (physical & chemical ‘barriers’) - Innate defence when ‘barriers’ penetrated, mediated by:
- Phagocytic cells
-Mononuclear phagocyte - macrophage - Polymorphonuclear phagocyte- neutrophil
- Natural Killer (NK) cells- Cytotoxic for tumour or host cells infected with virus
- Complement system (alternative pathway
What is the Complement system?
Aka complement cascade- part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation and attack the pathogen’s cell membrane.
- ~ 20 proteins
- Pro-enzymes requiring proteolytic cleavage to become active - Cascade allows amplification of response
- Complement activation normally occurs at localised sites,
- i.e. at the site of microbial infection
- Biologically significant effects
- C3 (third component)
- C5-C9
- First need activation
- Two pathways
-Classic pathway
-Alternative Pathway - Both form C3 convertase
-Cleaves C3 component - Then both proceed in identical fashion
- The Innate Immune system activates the Alternative Pathway
What are the 3 main biological functions of complement (system) ?
- Opsonization of micro-organisms
* Covalent binding of complement proteins to surface of microbes which will promote phagocytic uptake, e.g. C3 is a potent opsonin - Activation and attraction of the leucocytes in immune defence
* Complement cascade generates soluble fragments that can act upon
leucocytes, e.g. C3 / C5. - Lysis of target cells –
* Collection of Complement proteins Membrane Attack Complex (MAC) bind to microbial membrane increases permeability to bring about cell lysis (C5-C9)
- Deficiency in pathway – increased susceptibility to infections
What is opsonization?
An immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes
(how a pathogen is marked for phagocytosis)
What are they key cell types involved in the adaptive immune response?
- T-cell/lymphocyte mediated (Key cells types)
- During a primary adaptive immune response, both memory T cells and
effector T cells are generated – then secondary response - Helper T cells (TH), (bear the CD4 molecule)
- secreting cytokines that act to enhance other immune responses
- TH1 cells secretes cytokines that regulate the immunological activity and development
of a variety of cells, including macrophages and other types of T cells. - TH2 cells secrete cytokines that act on B cells to drive their differentiation into plasma
cells that make antibody. - Cytotoxic T cells (Tc)
- Kill target cells that are virus-infected by inducing apoptosis.
- Killing cell before the virus can complete its replication cycle results in the production of no
infectious particles
What is the Adaptive/ Acquired immune
response?
- Humoral Immune System / antibody-mediated
- B cells (or B lymphocytes) involved in production of antibodies
- Primary response (first exposure to antigen) B cells-
*
Plasma cells (generate antibodies)
-Memory cells
-Secondary response - Memory cells form plasma cells more quickly
- Much of response controlled by T lymphocyte
Pathogens
- Bacteria and viruses – different defence mechanisms
- Bacteria – lead to inflammation
- Viruses can replicate only inside host cells
- Released from cell – Damages cell
- causes the host cell to rupture, releasing virus particles
- virus particles surround themselves with a layer of host cell membrane and then bud off from the surface of the host cell
- Taking over cell - disrupt the cell’s metabolism so that the cell dies
Bacterial Infections
- Extra cellular
- Causes inflammation
Innate Response - Activate Complement
- Chemoattractants - attract leukocytes
from the circulation - Act as opsonins (activate phagocytosis)
- Degranulation of mast cells
- Chemoattractants
- Vasodilators (histamine)
- Complement cascade ends with
formation of membrane attack complex
(unencapsulated bacteria) - Cell lysis
Bacterial Infection
Innate Response
- Activate phagocytes
- Unencapsulated bacteria
- Macrophages begin to ingest
- Encapsulated bacteria
- Innate and acquired
- Antibodies coat capsule to aid
identification - Phagocytosis enhanced by
opsonins - Complement and antibodies See PMP 101 immune system lectures 2 and 3 for details of
innate and adaptive immune responsesNB: Capsule is found most commonly among gram negative
bacteria but some gram positive bacteria have capsule also
Viral Infections
Early stage - Extracellular phase:
* Innate and Adaptive Antibodies (Ab) (1)
* act as opsonins for macrophages
* Ab Bind viral particles prevent entry to target cells
Then if this stage not effective viruses enter cells –
Ab extracellular effects only
* Macrophages (2)
* Present viral fragments on surface
* Secrete cytokines
* Interferon – host cells make antiviral proteins (prevent
replication)
* Some stimulate NK and TH cells
* Helper T cells (TH) (3)
* Bind to viral antigen on macrophage
* Become activated
* Secrete cytokines that stimulate B lymphocytes and
cytotoxic T lymphocytes
- Memory B cells (4)
- Created by previous exposure
- Stimulated to develop into plasma cells
- More antibodies produced
- Cytotoxic T cells (5)
- Recognise infected host cells (viral antigen –
MHC I complex) - Secrete contents of their granules
- Induces cell to undergo apoptosis (cell suicide)
- Destroys cell and virus
- NK cells
- Some viruses cause host cells to withdraw MHC
I complex from surface - Recognised by NK cells
- NK cells induce these to under go apoptosis
- Destroys cell and virus
What is Pneumonia?
- Respiratory tract: common site of infection
- Causal organism: bacteria, viruses, fungi, parasites
- Inflammation of lung functional tissue and inflammatory exudate (pulmonary
oedema) - Lower respiratory tract infection
- Infection typically begins in alveoli, then spreads
- Impaired gas exchange
- Can cause Pleuritis (Pain on inspiration)
- Often no causative agent identified in many community acquired cases
- Streptococcus pneumoniae (S. pneumoniae)
- pneumonia, meningitis
Background of Pneumonia:
- Mostly disease of elderly or
immunocompromised host - Normal lungs sterile below first major bronchial division
- Pathogens reach lungs
- Direct inhalation into lower airways
- Aspiration of oropharyngeal contents
- Direct spread along mucosal membrane surface
(upper to lower respiratory tract system) - Originate from blood (Hematogenous sprea
What are the Clinical Presentations of Pneumonia?
Pulmonary:
* Fever
* Cough
* Tachypnoea (fast/shallow
breathing)
* Tachycardia
* Infiltrate on chest x-ray
Extra Pulmonary:
* Diarrhoea (Legionella)
* Clue to causative agen
