The course of a typical infection and adaptive immune responses can be divided into phases

If no innate immunity

The establishment of an infection depends on several factors:

Characteristics of the microorganism Number of organisms Mode of transmission (how and where they contact the host) Stability of the organism (in and outside of the host)

Almost all infections begin at an epithelial surface*

Skin and tight junctions usually prevent penetration

*skin or mucosal surface of the respiratory, gastrointestinal, and urogenital tract which are always exposed to microorganisms. Interstitial tissues are normally free of any microorganisms (sterile)

Most pathogens have developed defenses to partially escape destruction by the innate protective mechanisms listed in boxes 1 & 2 below

Most pathogens cause disease in only one or a few related species because the pathogens can adhere to epithelial surfaces of only a few species or can escape innate immunity of only a few species.

The course of the adaptive response to infection

How do infections progress in immune deficient individuals?

Adaptive immune response becomes important when innate immunity cannot deal with the infection within a couple of day

The results of an immune response vary depending on the individual and the pathogen and other factors (e.g, level of care).
After a primary immune response, usually there are no pathogens remaining. Sometimes the infection is contained but not elimintated (TB granuloma, herpes virus becomes latent, HIV is a retrovirus and mutates). Sometimes the pathogen or the immune response, or both, leave significant tissue damage (e.g., scaring, blindness). Often life-long immunity

Five major classes of pathogens

What governs whether a TH0 cell differentiates into TH1 or TH2? Pathogens influence cell of innate immunity to produce cytokines that affect TH0 differentiation into TH1 or TH2

NK cell

NK1.1 T cell is a T cell subset which expresses a surface molecule usually associated with NK cells and do not express normal TCR repertoire

TH1

TH2

IL-10

For example, TH1 inhibits TH2 and TH2 inhibits TH1.

T cell subsets produce cytokines that regulate development of other subsets

Thus most responses are dominated by either TH1 or TH2 and are not balanced responses

Cytokines influence the CD4 T cell subset development and this can be crucial for development of an appropriate immune response

Mice normally respond inappropriately to Leishmania and thus are killed by the parasite

Effector T cells change their adhesion molecules so they can migrate to the site of an infection. That is, adhesion molecules regulate trafficking

CD4+ T cells can license dendritic cells to activate CD8+ T cells (CTLs) (figure 8.28) but some CD8+ cells can be activated by dendritic cell in the absence of CD4+ T cells

CD8 T cells can be induced to secrete INF- in an antigen non-specific way

Peripheral lymphoid organs are the site of antigen-specific B cell activation [antigen binding (signal 1) and T cell help (signal 2)]

Protective immunity is the resistance to a pathogen that results from

infection or vaccination. It is due to an adaptive immune response which induced immunological memory of the pathogen. Usually, there are few or no symptoms associated with a infection when it is dealt with by protective immunity
Protective immunity consists of preformed immune components and immunological memory

Immunological Memory (maintenance of memory is probably

antigen-independent but there is evidence for antigen sequestration or reexposure to maintain memory)

Primary Vs. Secondary B Cell Responses

High quality

No increase in specificity

Primary Vs. Secondary Vs. Tertiary B Cell Responses

High quantity

High quality

Affinity maturation

Affinity maturation is a form of somatic selection (somatic evolution) where B cells, using their surface antibodies (BCRs), compete for limiting amounts of antigen. The B cell must compete with each other and with free antibody produced by plasma cells or plasmablasts. Only those B cells with the highest binding affinity will be able to bind to antigen and thus remain activated.

Some Characteristics of Memory B cells

Long-lived Memory B cells have high affinity antibody and high levels of MHC so they are efficient at acquiring antigens (signal 1) and ready to get T help (signal 2) Memory B cells have B7 on their surface so, maybe, they can activate or participate in activation of TH2 (memory) cells Memory B cell have usually switch class from IgM so they usually have other Ig isotypes on their surface (mostly IgG)

Memory T cells remain long after the virus infection is under control* or the viruses are gone

* The case shown here is the reactivation of a latent infection

Nave and memory T cell have different requirements for survival

Nave T cell require contact with MHC+self peptides for survival (like positive selection in the thymus)(too weak to activate the T cell)
Weak binding

Strong binding

Antigen encounter (signal 1) plus costimulation (signal 2) activates the T cell (proliferation and differentiation) Memory cells can come directly from the activated nave cells or from the effector cells Memory cells need cytokines but not contact with MHC+peptide for survival. This is different from the nave T cells (top panel) Memory T cells need MHC+self peptide to proliferate (weak interactions). These remain memory T cells and do not become effectors until they bind the MHC+the correct foreign peptide (strong binding).

Some differentiate into effector cells Most effectors die in a few days

Strong binding

Weak binding

proliferate

Effector T cell Nave T cell Memory T cell

Death

Nave B cell

Plasma cell Memory B cells

Death

We will skip subsets of memory cells (e.g. 10-17 and figure10.25

CD4 T cells are required for CTL (CD8) memory but not for primary CTL response

Original antigenic sin

When antigens have both epitopes that were seen before and new epitopes, the memory responses to the epitopes seen before will dominate and there may be little or no response to the new epitopes
Epitopes ACEF Epitopes ADEG

Epitopes ABCD