1. Medical Microbiology & Immunology
Guri Tzivion, PhD
Extension 506
BCHM 306: January 2015
Windsor University School of Medicine

2. Class Outline
Lecture 1: Immunology Introduction: Basic Concepts and Components of the Immune System, Innate Immunity
Lecture 2: Adaptive Immune Responses, Antigens, Antibodies and Cell-mediated Immunity

3. Class Outline
Lecture 3: Major Histocompatibility Complex, Transplantation and the Complement System
Lecture 4: Immunological Methods and Diagnostics, Hypersensitivity and Allergy

4. Class Outline Lecture 5: Tolerance and Autoimmune Diseases
Lecture 6: Tumor Immunity and Immunodeficiency

5. BCHM 306 MDIII Immunology Class 1 Immunology Introduction Basic Concepts and Components of the Immune System Innate Immunity

6. Two kinds of the immune system:
Innate immunity
Adaptive immunity

7. Innate Immunity or Nonspecific Immunity
Is present before any exposure to pathogens and is effective from the time of birth
Involves nonspecific responses to pathogens
Consists of external barriers plus internal cellular and chemical defenses
Nonspecific immunity is maintained by mechanisms that attack any irritant or abnormal substance that threatens the internal invironment.
Nonspecific immunity confers general protection rather than protection from certain kinds of invading cells or substances.
These defenses function the same way regardless of the invader or the number of times a particular type of organism invades.

8. Adaptive Immunity Also called specific immunity or acquired immunity
Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances
Involves a very specific response to the pathogen

9. Pathogens (such as bacteria, fungi, and viruses)
INNATE IMMUNITY (all animals)
• Rapid response
Recognition of traits shared by a broad range of pathogens using a small set of receptors •
Recognition of traits specific to particular pathogens using a large array of receptors
• Slower response
Barrier defenses:
Skin Mucousal membranes Secretions
Internal defenses:
Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response
Humoral response:
Antibodies defend against infection in body fluids
Cell-mediated response:
Cytotoxic cells defend against infection via cells
ADAPTIVE IMMUNITY (vertebrates only)
The Immune Response
Figure 43.2 Overview of animal immunity.

10. Innate Immunity of Invertebrates
In insects for example, an exoskeleton made of chitin forms the first barrier to pathogens
Their digestive system is protected by a chitin- based barrier and secreted lysozyme that helps in breaking down bacterial cell walls
The also have hemocytes circulating within their hemolymph that carry out phagocytosis

11. Phagocytosis Pathogen PHAGOCYTIC CELL Vacuole
Lysosome containing enzymes
Figure 43.3 Phagocytosis.

12. Innate Immunity of Vertebrates
Innate defenses include barrier defenses, phagocytosis and antimicrobial proteins and peptides
The vertebrate-specific defenses include: natural killer cells, interferons and inflammatory responses

13. Components of Innate Immunity:
Physical barriers
Phagocytic cells
Immunological surveillance
Interferons and and other cytokines
Complement system
Inflammation
Fever

14. Barrier Defenses
Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts
Mucus traps microbes and promotes their removal
Various body fluids including saliva, mucus, and tears provide hostile environment to microbes
The low pH of skin and the digestive system prevents growth of many bacteria

15. First line barriers to infection
Intact skin is a barrier that cannot normally be penetrated by bacteria or viruses although even very small abrasions may allow their passage
Likewise, the mucous membranes that line the digestive, respiratory, and genitourinary tracts bar the entry of potentially harmful microbes

16. First line barriers to infection: secretions
Secretions from sebaceous and sweat glands give the skin a pH ranging from 3 to 5, which is acidic enough to prevent colonization by many microbes
Microbial colonization is also inhibited by the washing action of saliva, tears and mucous secretion
All these secretions contain antimicrobial proteins
One of these, lysozyme, digests the cell walls of bacteria, helping in their destruction

17. Second line barriers
Microbes that penetrate the first line defenses face the second line defense, which depends mainly on phagocytosis (the ingestion of invading organisms by certain types of white blood cells).
Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins.
Phagocytic cells recognize groups of pathogens by surface receptors called Toll-Like Receptors (TLRs).

18. Toll-Like Receptors and select pathogen targets
EXTRACELLULAR FLUID
PHAGOCYTIC CELL
VESICLE
Lipopolysaccharide
Helper protein
TLR4
Flagellin
TLR5
CpG DNA
ds RNA
TLR9
TLR3
Innate immune responses
Figure 43.6 TLR signaling.

19. Innate immune response to injury
Pathogen
Splinter
Mast cell
Macro- phage
Capillary
Red blood cells
Neutrophil
Signaling molecules
Movement of fluid
Phagocytosis
Figure 43.8 Major events in a local inflammatory response.

20. There are several types of phagocytic cells:
Neutrophils engulf and destroy pathogens
Macrophages are found throughout the body but accumulate at injury sites and secrete inflammatory cytokines
Dendritic cells stimulate development of adaptive immunity
Eosinophils discharge destructive enzymes

21. Neutrophils
Constitute about % of all leukocytes (white blood cells)
Cells damaged by invading microbes release chemical signals that attract neutrophils from the blood
The neutrophils enter the infected tissue, engulf the microbes and destroy them
Neutrophils tend to self-destruct as they destroy foreign organisms, and their average life span is only few days

22. Eosinophils About 1.5% of all leukocytes
Contribute to defense against large parasitic invaders, such as the blood fluke, Schistosoma mansoni
Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from cytoplasmic granules

24. Monocytes & Macrophages
Constitute about 5% of leukocytes
Provide an effective phagoytic defense
They migrate into tissues from the blood and develop into macrophages
They extend long pseudopodia that can attach to polysaccharides on the microbe’s surface, engulfing the microbes by phagocytosis, and fusing the resulting vacuole with a lysosome

25. Monocytes vs M

26. DENDRITIC CELLS Originate in the bone marrow
Function as antigen presenting cells (APC).
Four types of dendritic cells are –
Langerhan’s cells
Interstitial dendritic cells
Myeloid cells
Lymphoid dendritic cells

27. Classes of innate immune cells
- Monocyte/Macrophage
- Dendritic cell (DC)
- Polymorphonuclear
granulocytes (PMN): Neutrophil, Eosinophil, Basophil
- Mast cell

28. Cellular innate defenses in vertebrates also involve natural killer cells
These cells circulate through the body and detect abnormal cells (cancer or virus-infected cells)
They release chemicals leading to target cell death, inhibiting the spread of virally infected or cancerous cells

29. THE INFLAMMATORY RESPONSE
Damage to tissue by a physical injury or by the entry of a microorganisms triggers a localized inflammatory response
One of the chemical signals is histamine
Histamine is released by circulating leukocytes called basophils and by mast cells in connective tissues

30. Cells of a tissue injured by physical damage or bacteria release chemical signals such as histamine and prostaglandin
In response to the signals, nearby capillaries dilate and became more permeable. Fluid and clotting elements move from the blood to the site and clotting begins.
Chemokines released by cells attract phagocytic cells from the blood
Phagocytic cells absorbe pathogens and cell debris promoting tissue healing

31. Antimicrobial Peptides and Proteins
Peptides and proteins function in the innate immune system by attacking pathogens or impeding their reproduction
Interferon promotes innate defenses by interfering with virus reproduction and activating macrophages
About 30 proteins make up the complement system, which causes lysis of invading cells and triggers inflammation

32. Inflammatory Responses
The inflammatory response, such as pain and swelling, is brought about by molecules released upon injury or infection
Mast cells release histamine, which triggers blood vessels to dilate and become more permeable
Activated macrophages and neutrophils release cytokines, signaling molecules that enhance the immune response and induce fever

33. Inflammation can be either local or systemic (throughout the body)
Fever is a systemic inflammatory response triggered by pyrogens released by macrophages and by toxins from pathogens
Septic shock is a life-threatening condition caused by an overwhelming or unbalanced inflammatory response

34. Evasion of Innate Immunity by Pathogens
Some pathogens avoid destruction by modifying their surface molecules to prevent recognition by the immune system or by resisting breakdown following phagocytosis

35. The lymphatic system

36. Peyer’s patches (small intestine) Lymphatic vessel Spleen
Interstitial fluid
Blood capillary
Adenoid
Tonsils
Lymphatic vessels
Thymus
Lymphatic vessel
Tissue cells
Peyer’s patches (small intestine)
Lymphatic vessel
Spleen
Figure 43.7 The human lymphatic system.
Lymph nodes
Appendix (cecum)
Masses of defensive cells
Lymph node

37. The various types of
immune cells