*Components of Adaptive Immunity

5A

What are the key features of adaptive immunity?

1. ability to distinguish self from non-self

2. pathogen specificity — species- or strain-specific

3. target diversity — designed to respond to vast # of epitopes

4. immunological memory — specialized long-living lymphocytes will be retained for quicker, more effective future responses

When is the adaptive immune system triggered?

Triggered when innate immunity cannot fully eliminate a pathogen.

Slower initial response compared to innate immunity, but more effective in long-term protection.

What is the flow of body fluids?

1. circulatory system (blood)

2. tissue (leaky capillaries) which drain into

3. lymphatic system

Contrast lymphatic vessels and blood vessels

Lymphatic vessels are similar to veins and arteries, but carry lymphatic fluid (lymphocytes)

Fluid is monitored for evidence of infection before being returned to circulatory system.

What would happen if lymph fluid cannot be returned to the heart?

Swelling, particularly in the legs, as gravity pulls fluid down.

What are the primary lymphoid tissues?

Bone marrow, thymus.

→ Makes the immune cells. Immune cells produced in bone marrow,.

→ T-cells mature in the thymus. B-cells mature in the bone marrow.

What are the secondary lymphoid tissues?

Spleen, lymph nodes.

→ stores immune cells until infection

→ Mucosa-associated lymphoid tissues (MALTs) found in places vulnerable to infection

What is bone marrow’s role in immunity?

• site of hematopoiesis

• hematopoietic stem cells constantly produce new immune cells

• body is always making new B- and T-cells

What is the spleen’s role in immunity?

• filters blood, not ECF (lymph nodes filter ECF)

• rich in macrophages and dendritic cells that remove pathogens and dying RBCs from bloodstream

• splenomegaly — englargement of spleen during infection

What’s the term for microbes entering the bloodstream?

Bacteremia/septicemia

How does the spleen distinguish old RBCs from young RBCs?

Older RBCs are less flexible and get trapped in splenic clefts.

Macrophages also detect signs of damage on RBCs.

Antigen

A substance that is able to react with a product of the adaptive immune response (lymphcyte, antibody).

Has the potential to trigger an immune response (not all do)

Immunogen

A substance that reacts with the immune products and is able to provoke an immune response (immunogenic).

Antigenicity

The intensity of antigen binding; depends largely on the 3D structure of the molecule.

Epitope

• The precise part of the molecule where the antibody or lymphocyte receptor attaches.

• the 3D shape more important that the amino acid composition

• antigenic determinants

Polyclonal antibodies

• A single antigen may have multiple epitopes recognized by different antibodies.

• Made by different populations of B-cells

Monoclonal antibodies (mAbs)

• Molecular biology tools that are produced in labs

• Highly specific to a single epitope; used as a therapeutic with minimal side-effects.

Haptens

• Extremely small molecules that, by themselves, can bind (antigenic) but poorly trigger an immune response (immunogenic)

• When fused with larger carrier complexes, immune response triggered.

• Hapten-carrier complex acts as immunogen, where hapten is antigenic determinant. (allergic reactions)

What is the role of haptens in sensitization?

First exposure sensitizes immune system; hapten recognized as antigenic determinant and no longer needs carrier.

Second exposure no longer needs carrier.

→ useful in vaccines

What are downsides of haptens?

Drug allergies — drugs may fuse to larger molecules to cause immune response against them

Anemia — drugs may fuse to RBCs, marking RBCs for destruction

Thrombocytopenia — same but with platelets

Autoantigen

Defects in the generation of immune products could lead to reaction against non-foreign ‘self’ substances. Should NOT be immunogenic.

→ autoimmune diseases

Alloantigen

Target antigens from other members of the same species. Only relevant in the case of tissue transplant (blood/organ)

→ ABO/Rh blood transfusion

Heterophilic antigen

Similar or identical antigens on unrelated organisms can cause abnormal immune function. 

→ M protein used to identify Streptococcus is also in heart tissue

Self antigen

During development, lymphocytes are tested for their responsiveness to ‘self antigen’

→ autoreactive lymphocytes are eliminated; self-reactive lymphocytes destroyed

Self antigen is mostly non-immunogenic

How are adaptive immune responses triggered?

Antigen presenting cells (APCs) display potential antigen molecules on their surface to assist in this initiation.

→ macrophages, dendritic cells, B-cells

Human Leukocyte Antigens (HLAs)

aka Major Histocompatibility Complex (MHC)

Cell surface proteins with a role in the adaptive immune system; survey and display antigens to T-cells.

Help distinguish between ‘self’ and ‘non-self’ 

MHC-I

Location: in all nucleated cells

Presents to: cytotoxic T-cells

Shows: antigens from proteins within cell

MHC-II

Location: only on professional APCs (macrophages, DCs, B-cells)

Presents to: helper T-cells

Shows: antigens from the environment (products of phagocytosis)

Describe the structure of MHC-I

Heterodimer made of heavy α-chain and smaller β-microglobulin.

Heavy α-chain has 3 domains α1, α2, α3 (encoded by HLA-A, HLA-B HLA-C)

Peptide binding groove = 3 α domains + β domain

Describe the structure of MHC-II

Heterodimer made of 2 chains: α-chain + β-chain

Encoded by HLA-DP, HLA-DQ, HLA-DR (each with α + β genes)

What is the clinical significance of HLA codominance?

• HLA matching is necessary for organs transplants

• Parents unlikely to have same haplotypes as one another or child

• Identical twins have same HLA haplotypes

• Most transplants from unrelated donors, needs immunosupressants to prevent rejections

→better HLA typing = less rejection

Haplotypes

The complete SET of HLA alleles on one chromosome — inherited codominantly from parent.

Isotypes

Each MHC has 3 isotype — the different GENES themselves

• MHC-I: HLA-A, HLA-B, HLA-C

• MHC-II: HLA-DP, HLA-DQ, HLA-DR

Allotypes

The specific VARIANT (allele) of each gene — what makes each persons HLA unique

• HLA-A2

• HLA-A24

• HLA-A17

Polymorphism

HLA genes are polymorphic — have many versions (alleles) of the each gene within a population.

→ structure of peptide-binding grooves of HLA-I and II will vary greatly among individuals

→ acts as molecular barcode to distinguish individuals

Why do we need such wide variety in MHC complexes?

To be able to respond to a wide variety of pathogens.