chapter 6 adaptive immunity “third line of defense” develops more slowly specific memory

Chapter 6

Adaptive Immunity

“third line of defense”

Develops more slowly

SpecificMemory

Adaptive Immunity

Antigens – “foreign or non self” (Ag= foreign proteins)◦ Viruses, bacteria, cancer, fungi or parasites◦ Noninfectious – pollens, foods, bee venoms◦ Drugs, vaccines, transfusions and

transplants

Adaptive ImmunityPrincipal cells: Lymphocytes

◦Accessory cells: APC & dendritic cells◦Effector cells

B cells → antibodies to blood → Ag T cells → attack Ag directly

Functionally◦ Regulatory◦ Effector

Specific◦ Each cell recognizes only ONE specific Ag

25-35% of blood leukocytes 99% reside in the lymph glands 60-70% of blood lymphocytes are T-cells

and 10-20% are B-cells

Foreign protein recognition:”surface receptor proteins-unique”◦ B-cells: membrane bound immunoglobulin◦ T-cells: self-recognition protein(major

histocompatibility complex)

“self from non self” Chromosome # 6 Two Classes

Class I *: endogenous pathogens -viruses & cancer Cytotoxic T cells… “must destroy me”

◦Class II : extracellular pathogens - bacteria & toxins Phagocytic cells: macrophages, dendritic cells, B

lymphocytes : Ag binds with MHC II Helper T

cell (CD4+) Human Leukocyte Antigens:WBCs

◦ Multiple allelles: A (120 genes) & B (250 genes)◦ Halotype: inherited unit

* all nucleated cells… not on RBCs

Class I… “all nucleated cells” (endogenous antigens)*

Function:present processed antigen to cytotoxic CD8+ T cells or

NK cells

“constant screening”

* Seen as abnormal…autoimmune disease

Class II …APC (dendritic, B cells, macrophage)

(exogenous antigens)

Function: presents processed antigen fragment to CD4+ T cells

effective interaction among immune cells*

*Figure:6-1

“Additional membrane bound proteins” Uses

◦ Aid the function of the immune cells◦ Define the functionally distinct subset of cells

CD4+ helper T cells – binding receptor: from APCs

CD8+ cytotoxic T cells- binding receptor: from all nucleated cells

Adaptive Immunity

Clonal diversity – 1st phase – fetus

◦ Recognition of millions* of foreign Ag◦ Large population of T & B cells◦ Develop in primary lymphoid organ (thymus,

bone marrow)◦ Migrate to secondary lymphoid organs

*108 or 100 million foreign antigens(proteins)

Generation of Clonal Diversity“primary lymphoid organ – fetus”

Lymphoid stem cell B and T cells recognize more than 108

antigens B lymphocytes – bone marrow “hormones”

– to secondary lymphoid organs* T lymphocytes – thymus “hormones” to

second lymphoid organs*

*lymph nodes & spleen

Secretory (Mucosal) Immune System

Lymphoid tissue that protects the external surface of the body

Ab present in tears, sweat, saliva, mucus and breast milk.

IgA dominant immunoglobulin◦ Prevent attachment and invasion of

pathogens

Adaptive Immunity“two arms”Humoral – B cells

◦ Antibodies – bacteria, viruses, and toxinsCell mediated – T cells

◦ Subpopulations React directly with Ag on cell surfaces –

NK(see next slide) Stimulate other leukocytes (cell to cell or

cytokines) T Cytotoxic cells – viruses infected cells and cancer

“lymphocytes” :functionally & phenotypically distinct from T cells, B cells, and monocyte-macrophages

◦ Automatically kill foreign cells: programmed

◦ No activation as with cytotoxic T cells

◦ Inhibition with contact of normal host MHC molecules

Antigens“molecule that reacts with antibodies or

receptors on B and T cells”

Immunogens-antibodies Epitope – antigenic determinant

(recognized) Paratope – Ag binding site (antibody or

lymphocyte)

Antigens Self-antigen – every cell*, genetically

determined (MHC), HLAs+

*glycoproteins – not RBC+ human leukocyte antigens

Tolerance

Humoral* Immune Response

Antibodies◦Immunoglobulins

◦Plasma cells◦Classes IgG, IgA, IgM, IgE and IgD

*fluid

Classes of ImmunoglobulinsIgG

◦Most abundant (80 to 85%)◦Transported across the placenta◦Four classes

IgA◦Two classes IgA1 – blood IgA2 – body secretions

Classes of Immunoglobulins• IgM– Largest– First Ab produced during 1° response to an Ag– Synthesized during fetal life

• IgD– Low concentration– Ag receptor on surface of early B cells

• IgE– Allergic responses– Parasite infections

Functions of Antibodies Direct effects

◦ Neutralization◦ Agglutination◦ Precipitation

Indirect effects◦ Opsonization◦ Complement

B Cell Antigen Receptor

Surface of B cell Consists

◦ Antigen – recognition molecule : IgM,IgG monomer

◦ Intracellular signaling molecules

Cell Mediated Immune Response• Mature T cells

–1.Cytotoxic (Tc) – attack and destroy directly

–2.Regulatory helper T (Th) – controls• Cell mediated• Humoral mediate• Suppressors (Ts)

–3.Memory cells“viruses, tumors, pathogens resistant to

neutrophils and macrophages”

T Cell Recognition of a Target Cell

T cell receptor complex◦ Antibody-like transmembrane protein◦ Accessory proteins for intracellular signaling

Antigen presentation molecules◦ By antigen presenting cells◦ Major histocompatibility complex (dendritic

cells*, macrophages, B-lymphocytes)◦ *Nobel Prize Medicine & Physiology 2011:

Beutler, Hoffman & Steinman

Functions of T-lymphocyte “Killing abnormal cell”

◦ Cytotoxic T lymphocytes (viruses, tumors) Attach to target cell : MHC-I molecules Appropriate CD molecules

Activate macrophages◦ Cytokines – chronic inflammation

Regulate immune response◦T-helper (Th) cell – humoral & cellular◦ T-suppressor cells – affects immune

response

Primary and Secondary Immune Responses

Primary◦Initial exposure◦ Latent period (B cell differentiation)◦ After 5 - 7 days – IgM antibodies detected◦ An IgG response follows

Primary and Secondary Immune Responses

Secondary◦ More rapid◦ Large amounts of Ab are produced◦ Rapid response - 2° to memory cells◦ IgM – similar to 1° response, IgG – greater

number Figure 6-15 Page 161

◦“MEMORY”

Active vs. Passive Immunity

Active Immunity◦ Antibodies or T cells produced after either a

natural exposure to an antigen or after immunization

Passive Immunity◦ Preformed Ab or T lymphocytes are

transferred from a donor to a recipient.◦ Example: IgG for hepatitis A exposure

: tetanus toxoid