1. Host Response to Infection

2. The Adult Human Comprises:
1014 Cells
1013 are Mammalian
9 × 1013 Microbes (at least)

3. Range of micro-organisms capable of causing infection & disease
Viruses
Bacteria
Fungi
Protozoa
Helminths
Arthropods
Prions

6. Host Response to Infection
Comprises 2 main arms:
(1) Innate immunity
(2) Adaptive (acquired) immunity
Many components, for example phagocytes &
cytokines, play a role in both responses

7. Innate Immune System
Initial response to microbial challenge (first line of defence)
Primitive in evolutionary terms but highly effective and can eliminate the micro-organism from the host
Non-specific (defends against any pathogen); does not depend upon prior exposure to the microbial agent; no change with repeat exposure; no memory
(A) Mechanical barriers; bactericidal substances; normal flora
(B) Humoral component (acute phase proteins, interferons, complement)
(C) Cell-mediated component (phagocytes, natural killer cells, eosinophils)

8. Innate Immune System
Ability to recognize structures that are unique to microbes (Pathogen-Associated Molecular Patterns, PAMPS) through Pattern Recognition Receptors (PRRs) on host cells & molecules that are part of the innate immune system
Lipotechoic acid (Gram +ve) and Lipopolysaccharide (Gram –ve) bacterial cell walls recognized by Toll-like receptors on macrophages leading to macrophage activation & cytokine production
Double-stranded RNA of replicating viruses recognized by toll-like receptors on NK cells leading to interferon production

9. Summary of TLR ligands recognized by TLR family

10. Adaptive Immune System
Initially slow to respond i.e. involved in clearing an infection
Subsequently prevents re-infection with the same pathogen
Specific components produced in response to a particular invader
Memory (faster, more vigorous immunological response on re-exposure)
(A) Humoral mediated– antibodies produced by plasma cells (transformed B-lymphocytes)
(B) Cell-mediated – T lymphocytes

11. Adaptive Immune Response & Immunological Memory

12. Host Response vs. Infection
Antibody (humoral mediated immunity) defends against viruses when outside cells, bacteria, toxins, fungi, parasites
Cell-mediated immunity defends against pathogens (all viruses, some bacteria, fungi and protozoa) that have entered into our own cells. Thus much more destructive as destroys both pathogen and host cell

13. Bacteria Prokaryotes (without a membrane-bound nucleus)
Mostly free living
Reproduce by binary fission
Usually have a cell wall
Size 
Classified by shape, size, staining characteristics but nowadays by genome sequencing
Can be killed by a vast array of antimicrobials

14. Bacterial Diseases
Many Infectious agents and many diseases Bacteria can Infect any part of the body
Cause disease due to
– Growth of the microbe in a tissue
– Produce Bacterial factors that are harmful to host
– Elicite an inflammatory response that causes damage
But also leads to acquired immunity

15. Steps of Bacterial Infection
1. Attachment of bacterium to host tissue
• Persistence and growth called colonization

16. Steps of Bacterial Infection 2
2. Invasion into deeper host tissues and production of toxins • Results in host cell and tissue injury

17. Steps of Bacterial Infection 3
3. Inflammation at site of invasion • Initiated by antibody binding to bacterium • Initiated by complement activation at bacterial surface • Initiated by wound healing mechanisms • All can activate complement pathways that alters vascular permeability and activates local macrophage and neutrophils (PMNs)

18. Inflammation at site of invasion

19. Factors that promote colonization, entry, and progression to disease

20. Factors that promote colonization, entry, and progression to disease
• Bacterial Aliginate
– Promotes adherence to host tissue
• Bacterial LPS and pilus
– Promote persistence by resisting complement and phagocytosis
• Bacterial Type III secretion system
– Deliver enzymes and toxins that
• injure host tissues or
• diminish host immune responses
• Includes signaling proteins, proteases, and superantigens

21. The defence mechanisms used depend on:-
Immunity to bacteria
The defence mechanisms used depend on:-
- Site of infection
- Structure of the invading bacteria
- How they cause damage
- Intracellular vs. extracellular location

22. How Can Bacteria Cause Damage?
Toxin production
Tissue invasion
Both
Clostridium tetani
Mycobacteria
Most bacteria

23. Immunity to bacteria Innate and adaptive immune systems work together.
In general, the innate response is important in preventing an infection becoming established, the adaptive subsequently in combating an established infection

24. Innate immune system can recognise and respond to common bacterial components
Not antigen specific but are protective responses generated by common often conserved bacterial components
Pathogen associated molecular patterns, (PAMS) recognised by cells of the innate immune system.
eg:-Lipopolysaccharide (LPS) produced by gram negative bacteria.

25. Innate Immune Effectors and Bacterial Infection

26. Adaptive Immune Response: Antibacterial Roles of Antibody
Action
How
Block adhesion
Ab to surface proteins
Block proliferation
Ab to surface receptors eg. iron
Cause phagocytosis
Bind bacterial surface and allow phagocytes to bind bacteria
Lysis, phagocytosis and inflammation
Activate complement
Neutralise toxic products
Bind toxins
Prevent tissue invasion and damage
Neutralise bacterial products and proteases

27. Immunity to extracellular bacteria by antibodies:
Antibodies and complement result in opsonization via FcReceptors (FcR) or Complement Receptors (CR) on M! and PMN.
Antibody can activate classical complement pathway resulting membrane attack complex (MAC) and opsonization via CR.
Antibodies can also trigger antibody-dependent cell mediated cytotoxicity (ADCC) by PMN with FcR and CR release proteases, nucleases, lipases.

28. Immunity to extracellular bacteria by antibodies

29. Immune System Function and Resistance to Bacterial Infection
Major mediators of resistance to extracellular bacterial infections is ANTIBODIES
Provide protective immunity by Killing live organisms through:
Opsonophagocytosis = promotion of complement mediated phagocytosis
Neutralizing bacterial toxins to prevent damage and intense damaging inflammatory responses

30. Mechanisms of Immunity to intracellular bacteria by CMI

31. Immunity to intracellular bacteria by cell mediated immunity (CMI)
Bacterial antigens present in the cytoplasm of infected host cell
– Processed via endogenous pathway and presented to CD8+ T cells (cytotoxic T lymphocytes or CTLs) on MHC class I.
Bacterial antigens present in the endosomes of infected host cell
– Processed via the exogenous pathway and presented to CD4+ helper T cells (TH) on MHC class II.
Bacterial antigens present on the surface of the infected host cell
can be bound by antibodies and targeted for killing by NK cells using ADCC

32. Do T Lymphocytes Have a Role in the Response to Bacteria?
T cytotoxic lymphocytes can kill infected cells
intracellular pathogens eg Mycobacterium tuberculosis
T helper cells produce cytokines or interleukins
more antibody production
Interferon  activates macrophages and increases bacterial killing, increases production of IgG used by phagocytes, increases cytotoxicity and CD8 T cell activity

33. Bacterial Virulence Factors: How they Thwart Host Immunity
• Virulence factors are anything that bacteria use to cause disease Examples: – Proteins, glycolipids, carbohydrates, teichoic acids, peptidoglycan, metabolites, enzymes, toxins • Impede the function of lymphocytes and granulocytes – Proteins, enzymes, and toxins • Overstimulate inflammation so normal defenses do not work – Glycolipids like LPS, cell wall structures like teichoic acids ad peptidoglycan, also enterotoxins and bacterial superantigens • Prevent phagocytosis – Carbohydrates like LPS side chains and capsular polysaccharides • Evade Complement mediated killing – Lots of ways..