Adaptive Immunity

Why Is Adaptive Immunity Important

• innate immunity contains infection but cannot fully clear pathogens until adaptive

• adaptive is much more specific then innate and has memory

• Adaptive immunity takes days while innate takes hours

Innate vs Adaptive

• Innate is first responder, non specific, limited and rapid

• Adaptive is more specific because can recognize specific antigens not just PAMPs and DAMPs, has memory and doesn’t have same response every time like innate, slower

  • offers long term protection and antigen specific elimination

Key components of Innate system vs Adaptive

Innate

• physical barriers

• phagocytes

• dendritic cells

• NK cells

• complement system

• cytokines

Adaptive

• B cells

• T cells

Relationship between innate and adaptive

• Innate immunity activates adaptive immunity

  • Involves dendritic cells presenting antigens to T cells

  • cytokines released from innate cells will shape the type of response adaptive immunity does

• Adaptive immunity enhances what innate immunity did

  • Antibodies improve opsonization

  • Activated T cells enhance killing that macrophage does

Major Components of Adaptive Immunity

• Antigen Presenting Cells (APCs)

• B lymphocytes (humoral immunity - antibodies circulating)

• T lymphocytes (cell mediated immunity - involve t cells rather than antibodies fighting infection)

APCs

• examples of APCs

  • Dendritic cells: professional APCs (showing pieces of pathogen to immune cells mainly t cells), immune activation

  • Macrophages: phagocytosis and antigen presentation - not professional cause have other roles like eating pathogens as well

  • B lymphocytes: are effectors and APCs

B lymphocytes

• Humoral immunity

• origin: bone marrow

• Function: antibody production and antigen presentation

T Lymphocytes

• cell mediated immunity

• origin: thymus

• Types

  • CD4+ T helper cells: carry out immune responses by differentiating into different phenotypes????

  • CD8+ Cytotoxic T cells: direct killing of infected or cancer cells

  • Regulatory T cells: maintain immune tolerance and prevent excessive immune response

Specific Definition of APCs

• specalized immune cells that capture, process and present antigens to T lymphocytes

• Dendritic cells are most powerful activators of naive T cells (haven’t been exposed to antigen yet)

Antigen Presentation

• antigen: molecule recognized by receptors on immune cells

• Epitope: specific site on antigen where a t or b cell receptor binds

  • B cells can recognize unprocessed/native antigens directly and don’t need help

    • can bind to free antigens

  • T cells can’t bind to unprocessed antigens directly, only recongize them when the antigens have been processed, chopped up and displayed by APC through their MHC proteins

B cell receptors

• 2 light chains at top, 2 heavy chain at bottom creating an antigen binding site

• recongize native antigens

T cell receptors

• alpha chain

• beta chain

• Both t and b cell receptors have 3 parts where the bottom part is transmembrane region, middle part is a constant region, and top part is variable region

Major Histocompatibility Complex (MHC)

• group of molecules found on cell surface that present antigens to T cells

  • peptide binding site is where they hold short sections of antigens to present

• These molecules located in a gentic “complex” have a major influence on transplantation success and name comes from there

• MHC molecules found in many different cell types not just immune cells

MHC 1

• Class 1

• found on all nucleated cells so NOT RBC

• presents to CD8+ Cytotoxic T cells responsible for direct killing

• Targets intracellular pathogens like viruses

  • peptides of antigen are processed inside cell and then loaded on MHC Class 1

MHC 2

• Class 2

• Found on APCs (DCs, Macrophages, B cells)

• Presents to CD4+ helper T cells

• Targets extracellular pathogens

Human Leukocyte Antigen (HLA)

• human version of MHC complex - instead of MHC say HLA in humans

• High polymorphism

  • HLA genes can drastically vary and everyone except identical twins rarely have identical HLA types making transplantation hard

• Immunogenicity

  • HLA antigens are immunogenic which means can strongly trigger an IR leading to organ rejection if donor and reciptent HLA types don’t closely match cause body will recongize organ transplanted as foregin and immune response

Two Arms of Adaptive Immunity

• humoral immunity

• cell mediated immunity

Humoral immunity

• B cells produce antibodies in blood/ lymphoid tissues that will bind to pathogen and eliminate them

• Targets extracellular pathogens outside of host cell

Cell Mediated Immunity

• driven by T cells

• T cells will directly kill pathogens or immune coordiantion

• targets intracellular pathogens and cancer cells

Components of Antibodies

• Fab Domain: variable and contains antigen binding site

• Fc Domain = mostly constant

• Heavy chains and light chains are linked through disulfide bridges

Types of Antibodies

• antibodies are immunoglobulins (secreted by B cells)

• Five types:

  • IgG

  • IgM

  • IgA

  • IgD

  • IgE

IgG

• most common circulating antibody

• 70-75% of total antibodies

• travels across placenta from mother to fetus

  • only one that can cross placenta

IgM

• first type that is secreted by plasma cells in response to a new antigen

• pentamer so highly effective at beginning cause 5 branches but not good binding affinity cause not specific

IgA

• crosses epithelial cells

• found in secretions like saliva and tears

• present in breast milk

IgD

• role unknown

  • possibly involved in RBC development

IgE

• fights parasites

• binds to receptors on eosinophils

• mediates histamine release

• involved in allergies

Cytokines are essiential for humoral immune response

B cell activation: Cytokines (IL-4, IL-5,IL-6) from T helper cells activate naive B cells essential for antibody production and allow the B cells to profilerate and differentiate into plasma cells

Isotope switching (important function of cytokine)

Cytokines guide B cells to switch from IgM to other antibodies

• Il-4 - IgE

• TGF-Beta - IgA (important for mucosal)

• IFN-Y - IgG (important for LT Immunity)

Plasma and Memory B cell Differentation

• IL-10, IL-21, help B cells differentiate into plasma cells (antibody producers) or memory B cells (long term immunity)

Antibody Affinity Maturation

• cytokines promote affinity maturation in germinal centers improving antibody binding strength

Immune Response regulation

• pro inflammatory cytokines (IL-1,IL-6) boost response

• anti inflammatory cytokines (IL-10) prevent excessive immune activation