1. understand how the appropriate lymphocytes are selected and activated and amplified

1. understand how the appropriate lymphocytes are selected and activated and amplified

2. understand how immune cells “talk” with each other via cytokines

3. compare and contrast activation and response of T and B lymphocytes

4. compare and contrast the activation and response of Th1, Th2, and T_C

5. understand the interactions between nonspecific and specific host defenses

6. understand how the specific immune response focuses the nonspecific response

7. understand the power of the secondary (anamnestic) immune response

B. Specific Defenses

• 
  = adaptive = acquired
  
• 
  3^rd line of defense – only one with antigenic memory
  
• 
  feedback into the nonspecific defenses – enhance the effectiveness of the non-specific defenses
  

Specific immune system has to:

1. 
   recognize
   
2. 
   activate
   
3. 
   respond
   

1. Overview

A specific interaction between an antigen and a receptor

Antigens incl:

***proteins (incl. proteins + carbos or lipids) (T and B)

***complex polysaccharides (B only)

***nucleic acids (B only)

Full activation of the specific defenses involves several different types of immune cells working in concert:

• 
  non-specific cells (antigen-presenting cells)
  
• 
  specific cells (lymphocytes)
  

Antigen-Presenting Cell (APC)

Specialized cells that present antigenic determinants in a way that can be more easily recognized by lymphocyte R

Most significant: dendritic cells (tissues) > macrophages > B cells

2 main types of Lymphocytes

• 
  T lymphocytes (T cells)
  
• 
  B lymphocytes (B cells
  

Lymphocyte receptors (R)

• 
  constant region – transmembrane
  
• 
  variable region – interacts with antigenic determinant
  

Antigenic determinant (= epitope) - small region of the antigen

• 
  linear or conformational
  
• 
  small in size
  

Presentation of antigenic determinant by an APC to a lymphocyte occurs in draining lymph nodes (surfaces, tissues) or spleen (blood)

1. receive and secrete cytokines

1à10⁴ – 10⁵ - occurs in lymphoid organs

effector – fight this time

memory – reserves, to be deployed in the future

c. Response – of activated effector sub-types

1. kill

secrete antibodies

2. Add in specifics
T Lymphocytes
2 categories of T cells by surface marker called Cluster Determinant
1. CD4 - 2 functional types

1) T helper cells = T_H - regulate the immune system by activating other immune cells

a) Subset Th1 – secrete -IFN – respond to intracellular pathogens - boost macrophages, NK, mature T_C; inhibit Th2

b) Subset Th2 – secrete IL-4 – respond to extracellular pathogens - stimulate B cells to proliferate and differentiate; inhibit Th1

2) T regulatory cells (=T_regs) - regulate the immune system by ¯the response
2. CD8 =T cytotoxic cells =T_C - attack & kill cells infected w/ intracellular pathogens

a. Antigen Recognition by Naïve Resting T lymphocytes

Class I - on the surface of all nucleated host cells

Class II – on the surface of APC
T_HR - recog. foreign antigen complexed w/ Class II MHC + co-stimulatory interactions (depend on who the APC is)

T_CR - recog. foreign antigen complexed w/ Class I MHC + co-stimulatory interactions

b. Activation of T lymphocytes

1. 
   Activation signal - cytokines, esp. IL from APC
   

2. 
   ↑ IL-2R and secrete/receive IL-2 à proliferation
   

3. 
   Differentiation into effector and memory cells
   

c. Response of Effector T Lymphocytes

• 
  enhance response - T_H
  

Subset Th2 – secretes IL-4 – stimulates B cell proliferation (down regulates Th1)

• 
  suppress response - Tregs
  
• 
  direct cell killing = cytotoxicity – T_C
  

Integration via Lymphocyte Recognition, Activation, and Response - Diagram

b. Activation of B Lymphocytes

1. 
   IL-4 from subset Th2 (also IL-2)
   
2. 
   Clonal expansion (= proliferation)
   
3. 
   Differentiation into effector (= plasma) and memory cells
   

c. Response of Effector B lymphocytes (=Plasma Cells)

Antibody Structure - Diagram

Actions of Antibody Molecules – focus the non-specific
1. direct – binding to antigen – interfere with receptor interaction – any microbe that uses specific attachment sites = neutralizing
***2. indirect – linking a bacterium to a phagocyte = opsonization (followed by phagocytosis)

	Opsonin	Rate of Phagocytosis
Microbe +phagocyte	none	-/+
	C3b	+
	CRP	+
	Ab
	C3b + Ab

3. indirect - link many small antigens together = agglutination (followed by phagocytosis)

Activation of Classical Complement Cascade - Diagram

Triggers –

Important molecules –

Consequences -

Timing –
Complement activation enhances phagocytosis and inflammation and leads to cell lysis.

Classes of Antibody Molecules

Feedback into the non-specific defenses; esp. complement, phagocytosis

Function of Memory Lymphocytes – the reserves - stronger response on secondary exposure to antigen

1. 
   are more memory cells then there were naive cells at the beginning of the primary response
   
2. 
   were primed to antigen during primary response so are able to bind more strongly to APC
   
3. 
   memory is usually long-lasting, years
   

Primary versus Secondary (= anamnestic) Response - Diagram

Misc.
Killer (K) cells
Rely on antigen specific antibodies BUT interact with antibody in a nonspecific way, participate in the non-specific interior defenses:
K cells include:

NK

macrophage

Complete:

T_H

function –

recognition –

activation –

response – Th1 -

-- Th2 –

function –

recognition -

activation –

response –
T_reg

function –

recognition -

activation –

response –
B Lymphocyte

recognition –

activation –

response –

List the Specific Interior Defenses important against Viruses

When Steve. awoke on the second morning, his condition was clearly deteriorating. The first thing he noticed was that the small area of redness and swelling had extended to include his entire hand, with the margin of redness now visible just above his wrist. Faint red streaks had appeared along the inner part of his arm and tender lumps were noticeable below his elbow and under his arm. His fever seemed higher than the night before, and he felt too weak to walk.

2. Steve began to improve within 4-5 days of initial infection. How could antibody have played a role in resolving Steve’s symptoms within this time frame?