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Flashcards in Path & host Deck (38):
1

Pathogenicity factors

How likely is an organism to cause an illness?
1. Infectivity, ability to become established on or within host
2. Virulence, ability to cause harmful effects once established

2

Infectivity factors

- Attachment e.g. E.coli have P-fimbriae
- Acid resistance e.g. H.pylori, has urease which makes ammonia from urea

3

Virulence factors

- Invasiveness, reproduces rapidly
- Toxin production, infects immune system
- Exotoxins released extracellularly by the microorganism
- Enterotoxins are exotoxins which act on the GI tract
- Endotoxin is structurally part of the Gram negative cell wall, Lipid A is the nasty bit
- Evasion of immune system
- These are specific to strains, not species

4

Streptococcus pyogenes

- Highly invasive
- Enterotoxin, superantigen
- Necrotising fasciitis
- Cellulitis
- Connective tissue breakdown by enzymes
- Fibrinolysis - enzymatic breakdown of fibrin in blood clots
- Stimulate division of T cells in the absence of specific antigen
- Overwhelming cytokine production - toxic shock

5

Tetanus

- Clostridium tetani
- High virulence
- Infects dirty wounds
- Toxin production, binds to nerve synapses, inhibits release of inhibitory NTs
- Death by respiratory paralysis
- Rx by debridement and abx and antitoxin

6

Cholera

- Vibrio cholera
- High virulence
- Enterotoxins
- Colonises small intestine
- Toxin production, increases cAMP levels, inhibits uptake of Na+ and Cl- ions. Stimulates secretion of Cl- and HCO3- ions.
- Passive, massive outflow of H2O
- Death by dehydration
- Rx - rehydration

7

Staph aureus

- Highly virulent
- Enterotoxin
- Stimulate division of T cells in the absence of specific antigen
- Overwhelming cytokine production - toxic shock

8

E.coli

- O157 is the nasty one
- Induces severe uncontrolled host repose
- Cytokine production
- Fever, rigors, hypotension, tachycardia, collapse

9

Mechanisms of viral pathogenesis

- Cell destruction following virus infection, death of T4 cells by HIV
- Virus-induced changes to cellular gene expression, cellular transformation by tumour viruses
- Immunopathogenic disease, Influenza A, induced myocarditis

10

Sites of viral entry

- Conjunctiva
- Arthropod, insect bite
- Capillary
- Respiratory tract
- Alimentary tract
- Skin
- Urinogenital tract

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Types of viral infection

- Acute
- Latent
- Chronic
- Tumour virus infection
NB: symptoms arise at peak of virus in body

12

Acute viral infection

- Localised, specific to site
- Development of viraemia can go to other tissues

13

Examples of acute viral infections

- Influenza A, resp. infection. Virus infects cells of respiratory tract, destruction of respiratory epithelium, altered cytokine expression leading to fever

- Enterovirus. Virus is normally excreted in faeces but if viraemia occurs then it can get into non-neuronal tissues and neuronal tissues.

14

Enterovirus examples

Poliomyelitis, aseptic meningitis, myocarditis, pancreatitis, respiratory infections

15

Latent viral infections example and life cycle

- Herpes simplex virus: primary infection in epithelium
- Virus migrates to ganglia and stays latent in nucleus, no virus replication
- Stimulus occurs e.g. stress, life events, immunosuppressants, sunlight
- Virus migrates back to epithelium and it is released, results in replication

16

Tumour virus infections examples

- Papilloviruses: cervical carcinoma
- Retroviruses: lymphomas and leukaemieas, causes the cells to be transformed from normal:
1. Virus infects cell, virus nucleic acid, as DNA, integrates into cellular genome
2. Virus causes changes in cellular gene expression
3. Uncontrolled cell multiplication and tumour formation

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Antigenic drift

Gradual evolution of viruses to generate antigenic variants
You might have partial immunity

18

Antigenic shift

Significant changes in virus antigenic structure
Complete change, no immunity
Avian flu and swine flu are examples where non-human hosts for influenza A play a key role in new types of virus

19

Define pathogen

Organism which can cause disease

20

Define commensal

Organism which is part of the normal flora e.g. E.coli in gut, Staph aureus in nose, axilla

21

Examples of innate immunity

- Skin, gastric acid, muco-ciliary escalator
- Phagocytic cells
- Other white cells (T cells, B cells, these aren't phagocytic)
- Opsonisation

22

Phagocytic cells examples

- Polymorphs (acute, short lived): neutrophils, eosinophils, basophils
- Macrophages (chronic, long lived): monocytes in blood mature into macrophages
- Fixed macrophages (liver, spleen, lymph nodes) of the mononuclear phagocytic system
- Free macrophages in the tissues
- Mononuclear phagocytic system

23

Mononuclear phagocytic system examples

- Spleen clears blood (why you get overwhelming Strep pneumoniae infection in splenectomy)
- Liver clears entero-hepatic circulation
- Regional lymph node drain peripheral sites

24

Opsonisation

- How a phagocyte recognises and destroys an antibody
- Phagocytic cell has receptors for both
- Efficiency of phagocytosis is greatly improved
- Important for capsulate bacteria as you can get around the problems with phagocytosis and intracellular killing e.g. Strep pneumoniae and haemophilus influenzae

25

Process of phagocytosis

1. Phagocytosis (ingestion), cell engulfs particle in vesicle
2. Organism held in phagosome
3. Fusion with lysosome, in case of macrophage
4. Phagolysosome is formed
5. Intracellular killing

26

Organisms resistant to phagocytosis

- Capsulate organisms e.g. strep pneumoniae
- Mycobacterium tuberculosis is resistant to intracellular killing

27

Acquired immunity

- Specific response to antigen concerned
- Immunological memory created
- Humoral and cellular
- Each organism is a complex mixture of antigens
- Each antigen is a mixture of epitopes, bits that recognise immune system

28

What do antibodies do?

1. Neutralise bacterial toxins
2. Neutralises viruses in viraemic stage
3. Prevent adherence of mircoorganisms
4. Opsonises capsulate organisms (Strep pneumoniae, Haemophilus influenzae)
5. Useful means of diagnosis with serology

29

5 classes of immunoglobulins

- IgM: eliminates pathogens with B cells before there are any IgG cells
- IgG: majority of antibody-based immunity against invading pathogens
- IgA: mucosal immunity
- IgE: allergy and helminth infection
- IgD: antigen receptor on B cells that have not been exposed to B cells

30

B-lymphocytes

- Differentiate into plasma cells when they recognise a specific epitope
- B-lymphocytes require T cell help

31

Monoclonal antibody vs polyclonal antibody

Monoclonal -from one clone of plasma cell which has specificity for a single epitope
Polyclonal antibody - multiple specificity

32

Antibody and complement in infection

1. Opsonisation by complement
2. Lysis of Gram negative organisms by complement
3. Complement cascade by-products are chemotactic (attract polymophs)

33

Humoral immunity

- Found in body fluids
- Mostly used in bacterial infection
- Extracellular
- Acute inflammation
- Neutrophilia

34

Cell mediated immunity

- Combats intracellular infection (viruses, certain bacteria and fungi)
- Lymphocytosis
- e.g. Mycobacterium tuberculosis is resistant to intracellular killing, Legionella pneumonphila and Candida albicans

35

How cell mediated immunity works

- Macrophages 'present' the antigen and this stimulates the T-cells
- Two T cells: CD4 helper and CD8 suppressor and cytotoxic cells
- Cytokines are produced and control the response

36

Define colonisation

- No signs or symptoms
- MRSA can cause infection or colonisation
- Infection is opposite as you get signs and symptoms

37

Define asymptomatic infection

Infection without symptoms

38

Define latent infection

Asymptomatic infection capable of manifesting symptoms under particular circumstances or if activated