Anatomic and cellular basis of immune response Flashcards
Organization of Immune system
What 2 overlapping compartments
• Lymphoid system
Central and Peripheral
• Reticuloendothelial system
Circulating monocytes
Resident macrophages
Macrophage like cells –
dendritic cells (lymp nodes),
glial cells (nerve)
Langerhan’s cells (skin)
Functions of immune system
Lymphoid organs
- protection against foreign agents
- orchestrate functions of immune system – cytokines (lymphokines)
RES
- phagocytosis & intracellular killing
- recruiting inflammatory cells by cytokine (monokines) - antigen presenting to lymphocytes to initiate antigen-
specific immunity
Structural organs/tissues
Two groups of lymphoid organs
• Primary - thymus and bone marrow
• Secondary - lymph nodes, spleen, mucosal & submucosal tissues of alimentary & respiratory tracts
Types of lymphocytes
• T and B cells - responsible for antigen-specific immunity
T cells – Cell mediated immunity
B cells – Humoral immunity - antibody formation
• NK cells - cytotoxic to tumor cells & cells expressing foreign antigens
Development: Pluripotent Bone Marrow Stem Cells
Immune System cells are derived from pluripotent hematopoietic stem cells in the bone marrow.
bone marrow➡️ pluripotent stem cell➡️ lymphoid progenitor cell ➡️ B cell precursor ➡️ Mature B cell
Leukocytes
White blood cells that provide either innate or specific adaptive immunity
Myeloid Cells
Myeloid Cells: First line of defense, non-specific innate immunity
• Neutrophils
• Eosinophils
• Basophils/Mast cells
• Monocytes/Macrophages/Dendritic Cells
Lymphoid Cells
Lymphoid Cells: Humoral and Cell Mediated specific immunity
• B Lymphocytes
• T Lymphocytes
• Natural Killer Cells (innate immunity)
Bone marrow
• Site of hematopoiesis & B lymphocyte development
• is a loosely-organized group of cells in central soft tissue portion of bones surrounded by calcified matrix
• Hematopoietic stem cells- development of all blood cells after about the seventh month of gestation in humans
• B lymphocytes, granulocytes, monocytes and erythrocytes all develop to maturity in the bone marrow before they are released
• Pro T lymphocytes (immature T cells) are released into the bloodstream before final maturation
what structure of B cell
marker and its function
surface ig- antigen specific recognition
MHC , class II - Antigen presentation
B7-1 & 2- T cell activation
CD40- receives activation signal from t cells
CD19-21 - unique B cell markers
mitogen receptor - binding and activation by bacterial products
Activation of B Lymphocytes
Activation of B Lymphocytes
• Activation of B cells into antibody secreting cells is antigen-dependent.
• Specific antigen binds to surface Ig molecules which triggers differentiation into plasma cells.
• Interaction with T cell secreted factors triggers isotype (class) switching.
Clonal selection theory
Clonal selection theory
• Every individual has numerous clonally derived lymphocytes, each arising from a single precursor
• Each clone is capable of recognizing and responding to a distinct antigenic determinant
• Antigen selects a specific pre-existing clone and activates it, leading to proliferation and its differentiation into effector and memory cells
thymus
• Bilobed organ - site of T lymphocyte development
• 2 types of tissue - reticular cells(stromal cells) and developing T
lymphocytes (T cells) are randomly situated in clusters
• Cortex - area of intense T cell development. Pro T cells develop their antigen-receptors (TCRs) & their (CD4 & CD 8) co-receptors to become immature “double-positive” T lymphocytes
• Corticomedullary junction - region between cortex & medulla where self-responsive T cells are eliminated by apoptosis by interaction with antigen-presenting cells (APCs)
• Medulla -“staging” area where mature “single-positive” T lymphocytes migrate before being released
T Lymphocyte types
T Lymphocytes develop in thymus
• T helper cells (Th) can synthesize and secrete cytokines and function to regulate immune responses (both antibody and cell-mediated) when appropriately stimulated during immune responses
• T cytotoxic cells (Tc) are mature precursor cells that, as a result of a cell-mediated immune response, differentiate into cytotoxic T lymphocytes (CTL) which mediate cellular immunity vs virus-infected cells and tumor cells
Types of Helper T Cells
• Th1
– participate in CMI. They are essential for controlling such intracellular pathogens as viruses and certain bacteria, e.g., Listeria & M. tuberculosis
• Th2
– These provide help for B cells, are essential for antibody-mediated immunity. Antibodies are needed to control extracellular pathogens
lymph nodes - structures and functions
• Bean-shaped, encapsulated nodules at junctions of lymphatics at strategic areas • •Filters particulate & soluble molecules in lymph for immune system stimulation
3 types of tissue lymph nodes
3 types of tissue
1.Cortical (cortex) tissue:
- Characterized by lymphoid follicles (LF)
- Outer region - lymph drains from afferent lymphatics
- B cells are primary lymphoid cells (few T cells & follicular dendritic cells) - Germinal centers develop within LF as result of antibody responses
2.Paracortical (paracortex) tissue:
- Located in intermediate region & partially surround lymphoid follicles - T cells are primary lymphoid cells (few macrophages & dendritic cells) - On ag stimulation migrate to lymphoid follicles to deliver cytokine
3.Medullary (medulla) tissue:
- Located in central region - loosely-organized aggregate of phagocytic cell - Macrophages & dendritic cells (APCs) are primary lymphoid cells
(variable numbers of plasma cells, active immune responses)
- APCs migrate into paracortical region when they have processed antigen & are presenting immunogen fragments on their ACRs to T cells to initiate IR
spleen
White pulp circular mainly made of lymphocyte. functions as part of specific immune defense
Red pulp surrounds white pulp - contains mainly RBC & macrophages. The main function is to phagocytize old RBC
MALT
• Mucosa-associated lymphoid tissue - lymphoid tissue is found at other sites, most notably gastrointestinal, respiratory & urogenital tract - GALT, BALT & VALT
GALT
Gut associated lymphoid tissue, part of MALT
Tonsils
Located at the back of mouth. Made of lymph tissue and help to fight off infection. Largest in childhood & gradually shrink throughout life
adenoids (Waldeyer’s ring).
Ring of lymphoid tissue located in lingual, palatine and nasopharyngeal.
Prominent during childhood
Homogenous lobulated soft tissue
Peyer’s patches
Lymphoid aggregates in appendix , small & large intestine Lymphoid tissue accumulating with age in the stomach Small lymphoid aggregates in the oesophagus
Diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut
Cutaneous-associated lymphoid tissue
• Epidermis contains intra-epidermal lymphocytes • Langerhans (dendritic) cells can process and
present antigen to T cells.
• Even migrate to local lymph nodes after phagocytizing
exogenous antigen
Terminology: Cluster Of Differentiation (CD)
• Cell surface molecules are identifiable by monoclonal antibodies
• In humans, these molecules have been given number designations • CD describes cluster of antigens, with which antibody reacts
• The number describes the order in which it was discovered
CD-specific monoclonal antibodies have been useful for:
• Determining functions of CD proteins
• Identify distribution of CD proteins in different cells in normal individuals
• Measure changes in proportion of cells carrying these markers in patients with disease (e.g. decrease in CD4+ T cells is a hallmark of HIV infection).
• Developing therapeutic measures for increasing or decreasing the numbers or activities of certain cell populations
The Major Histocompatibility Complex
• The Major Histocompatibility Complex (MHC) is a locus on a chromosome comprised of multiple genes encoding histocompatibility antigens
• The Histocompatability antigens are cell surface glycoproteins which play critical roles in interactions among immune system cells
• MHC genes are highly polymorphic
MHC - Function
• The transport molecules are called Major Histocompatibility Complex (MHC) proteins. Without these, there would be no presentation of internal or external antigens to the T cells
• MHC proteins allow T cells to distinguish self from non-self
• Fundamental role: regulate immune responses
Other roles: disease defense, cancer, autoimmunity and graft rejection
MHC Molecule Organization
3 Classes of MHC Encoded Molecules
3 Classes of MHC Encoded Molecules
• Class I participate in antigen presentation to CD8+ lymphocytes (CTL) - all nucleated cells express Class I MHC
• Class II participate in antigen presentation to CD4+ lymphocytes (T helper) - macrophages, dendritic cells & B cells
• Class III MHC include complement proteins, tumor necrosis factor, and lymphotoxin.
Human HLA Complex
• Class I region consists of HLA-A, HLA-B, and HLA-C loci.
• Class II region consists of the D region which is subdivided into HLA-DP, HLA-DQ, and HLA-DR subregions.
• Class III molecules are encoded by genes located between those that encode class I and class II molecules.
