Introduction

Question 1

Immune Response

Definition

Answer 1

• Maintain a state of homeostasis such that when the system is perturbed by a foreign invader (external or internal) an adequate response is generated to control the invader
• Then the system returns to equilibrium.
• It’s memory of that particular invader is retained so that a more rapid and heightened response will occur should the invader return

Question 2

External Threats

Answer 2

1. Microorganisms
   
   • Bacteria
   • Viruses
   • Fungi
2. Parasites
   
   • Protozoa
   • Worms
   • Ectoparasites
3. Mechanical or chemical trauma

Question 3

Internal Threats

Answer 3

1. Cancerous cells
2. Abnormal cells
3. Old or damaged cells

Question 4

Mechanisms of Defense

Answer 4

1. Exterior Barrier
2. Innate immune response
3. Adaptive immune response
4. Memory
   
   • Prevents reinfection or recurrence of illness
   • Maintained by adaptive immunity
   • Functionally combines both innate and adaptive immunity

Question 5

Exterior Defense Mechanisms

Answer 5

Provides a natural barrier that:

1. Prevents microbial colonization
2. Prevents host invasion

Microorganisms generally need to adhere to/penetrate host tissues and proliferate at that time to induce disease.

Question 6

Mechanical Barriers

Answer 6

Contribute to defense by inhibiting attachment and penetration of infectious agents.

• Skin
• Mucus
• Cilia lining mucosa (mucociliary elevator)
• Mechanical
  
  • Coughing
  • Sneezing
  • Peristalsis

Question 7

Chemical Barriers

Answer 7

Numerous components of bodily secretions contain microbicidal factors.

• Sweat and sebaceous secretions
  
  • Contain lactic acid and fatty acids
• Lysozyme
  
  • Present in tears, saliva, and nasal secretions
  • Hydrolyzes bacterial cell wall
• Acidic environments
  
  • Urine and vaginal secretions
  • Hydrochloric acid in stomach
• Lactoferrin and transferrin
  
  • Iron chelators
• Defensins
  
  • In the lung and GI tract
  • Damages microbial membranes

Question 8

Bacterial Interference

Answer 8

• Normal flora colonizes:
  
  • Upper respiratory
  • Lower GI
  • Reproductive tracts
  • Skin
• Competes with pathogens for nutrients and for attachment sites on epithelial or mucosal surfaces
• Potent barrier to the establishment of infection by pathogens

Question 9

Microbial Invasion

Answer 9

Pathogens can evade, overwhelm, or penetrate a barrier.

After entry into the host it begins to replicate.

Body generates an immune response.

Question 10

Immune Response

Overview

Answer 10

Innate Immunity

• Ready to function prior to exposure to the threat ⇒ rapid response
• Attempts to control and/or eliminate the threat
• If unable to eliminate the threat, the goal is to keep the body alive long enough for the adaptive response to occur

Adaptive Immunity

• Activated if innate immunity has failed to eliminate the threat
• Threat has bypassed an “activation threshold”
• Includes mechanisms that require days to weeks to become fully functional
• Usually capable of eliminating the threat
• Establishes long-term memory

Question 11

Innate Immunity

Overview

Answer 11

• Functions by means of pre-existing antimicrobial molecules and cells
• Can resolve most insults
• Only has a few types of recognition molecules that recognize common motifs to many different pathogens
• Can use components of the adaptive immunity to target their immune response
  
  • Antibodies & Cytokines

Question 12

Innate Immunity

Components

Answer 12

1. Phagocytic cells
   
   • Neutrophils
   • Macrophages
   • Natural killer (NK) cells
2. Several cytokines
3. Complement
4. Multiple plasma proteins

Question 13

Innate Immune Response

Goals

Answer 13

1. Kill/remove the threat
2. If unable to remove threat, amplifies and stimulates the immune response
3. Prevent spread of the threat
4. Prepare for the adaptive immune response

Question 14

Cytokine

Definition

Answer 14

• A mediator that influences the growth, differentiation, or function of cell types inside and outside of the immune system
• Made by cells of the immune system and other cells in the body
• Usually a soluble glycoprotein that binds to specific receptors to induce signaling

Question 15

Tissue Macrophages

Answer 15

There are two major types of tissue macrophages:

• Resident macrophages
  
  • Microglia
  • Kupffer cells
  • Alveolar macrophages
  • Osteoclasts
• Proinflammatory macrophages
  
  • Recruited from the blood during an immune response

Question 16

Neutrophils

(PMNs)

Answer 16

• Granulocytes that circulate in the blood
• Migrate quickly in response to local stimulation or invasion by a microorganism
• Critical to immune defense against extracellular bacteria & other threats

Question 17

Antigen

Answer 17

Any molecule that can bind specifically to an antigen receptor (e.g. antibody, TCR)

Pathogens are usually composed of many repeating antigentic components.

Question 18

Epitope

Answer 18

The site on an antigen that is bound by an antibody or TCR

(a.k.a. antigenic determinants)

Many/most antigens have more than one epitope

Question 19

Methods of Recognition

Answer 19

• Both Ig and TCR contain:
  
  • a variable antigen-binding domain
  • a constant region
    
    • Important in anchoring it to the cell
    • Gives it certain effector properties
• Characteristics of B and/or T cell responses:
  
  • Specific for initiating antigen
  • Each receptor varies slightly in structure giving it a different reactivity
  • Each B or T cell only expresses a single antigen receptor

Question 20

Immunoglobulins

(Ig)

Answer 20

Expressed by B-cells:

• B cell receptor (BCR)
  
  • Membrane bound Ig that determines the antigen specificity of the B cell
  • BCR can bind free antigen (native and/or denatured)
    
    • Protein
    • Polysaccharide
    • Lipid
    • Nucleic acid
• Antibodies (Ab)
  
  • Soluble forms of immunoglobulins
  • Secreted by plasma cells
  • Exerts different effector functions

Question 21

TCR

(T cell receptor)

Answer 21

• Membrane-bound antigen receptor expressed by T-cells
• TCR cannot bind to free antigen
• Only recognizes peptide antigens presented by major histocompatibility molecules
  
  • Class I MHC
  • Class II MHC
• Means T-cells are stimulated by host cells expressing MHC and foreign antigens but not free antigen

Question 22

Lymphoid Organs

Answer 22

1. Primary lymphoid organs
   
   • generative organs
   • B lymphocytes (B cells) - bone marrow
   • T lymphocytes (T cells) - thymus
2. Secondary lymphoid organs
   
   • Highly organized tissues that promote the interaction between antigen, T cells, and B cells.
   • Naive T and B cells are usually activated here then proliferate, differentiate, and promote effector functions
   • Includes:
     
     • Lymph nodes
     • Spleen
     • MALT (mucosal-associated lymphoid tissue)
       
       • BALT (bronchial-associated lymphoid tissue)
       • GALT (gut-associated lymphoid tissue)

Question 23

Clonal Proliferation

Answer 23

• Usually a threat will activate the few cells that can recognize it out of the millions of different antigen receptors
• Cells stimulated to divide, proliferate, and differentiate into effector cells.
• Daughter clones have the same antigenic specificity as the parental cell.

Question 24

Helper T-cells

(T_H)

Answer 24

• Express CD4⁺ markers
• Synthesize cytokines
  
  • Modulate the immune system
  • Helps immune system to function
• Critical role in promoting most adaptive and many innate immune responses
• Promotes immunity to both intracellular and extracellular threats

Question 25

Cytotoxic T Cells | (T_C)

Answer 25

* Express CD8⁺ surface markers * Kill cells by direct cell-cell contact if TCR is properly engaged * Produce a limited cytokine profile * Plays a major role in immunity against intracellular threats * Viruses * Abnormal cells/cancer * Some intracellular bacteria

Question 26

B lymphocytes

Answer 26

* Produce antibodies that plays a role in: * Eliminating extracellular microorganisms * Neutralizing soluble toxins

Question 27

Antibody Isotypes

Answer 27

* There are different major classes of antibodies. * Each isotype can be characterized by: * Structure * Location * Effector functions * Some isotypes promote unique intracellular actions through Fc receptors

Question 28

Extracellular Bacteria Immune Response

Answer 28

* Complement * Macrophages * Neutrophils * Proinflammatory response * Antibodies (adaptive) * +/- T_H cells (adaptive)

Question 29

Intracellular Bacteria Immune Response

Answer 29

* Macrophages * T_H cells (adaptive, IFN-γ)

Question 30

Viruses Immune Response

Answer 30

* Select cytokines * Type I Interferons (IFN-α and IFN-β) * Natural killer cells (NK cells) * Cytokine production by T-helper cells (adaptive) * Killing by cytotoxic T-cells (adaptive) * Less of a role: * Complement * Macrophages * Neutrophils * Proinflammatory cytokines

Question 31

Helminthic Parasites Immune Response

Answer 31

* Eosinophils * Mast cells * Basophils * IgE (adaptive immunity) * T_H cells (adaptive)

Question 32

Phases of the Immune Response

Answer 32

1. **Recognition Phase** * Innate Immunity * Receptors bind common pathogenic motifs * lipopolysaccharide (LPS) * mannose * C-polysaccharide * Recognizing other components of the immune response: * antibodies * cytokines * products of innate immunity * Adaptive immunity * Antigen specific receptors 2. **Amplification Phase** * Innate Immunity: * Cascades (complement) * Secretion of soluble mediators * Cytokines * Acute phase proteins * Recruitment of an "army of cells" * Neutrophils * Adaptive Immunity: * Lymphocyte proliferation and differentiation into effector cells 3. **Effector Phase** * Elimination of antigen by one of many mechanisms * Phagocytosis * Lysis * Neutralization * Killing by cytotoxic T-cells 4. **Termination Phase** * A number of mechanisms down regulate the immune system after antigen has been removed * Very important because an improperly regulated immune response can cause extensive tissue damage 5. **Memory** * Adaptive * Facilitates innate processes * Long-lived memory T and B cells are generated * Memory cells have lower threshold for activation * React faster * Shows amplification * "Mature" response where Ab generated * Residual components (antibodies) are immediately available