Summary Mechanisms of Disease 1: T1-T3 Learning Objectives

M.V.D.


LEARNING OBJECTIVES MOD1

THEME 1

1. Immune System Defense Mechanisms:

 Understand and describe the anatomical, chemical, and physical barriers
that serve as the first line of defense against pathogens.
o Anatomical
 Skin: mechanical shield against m.o.'s, with slightly acidic
surface
 Mucous membranes: respiratory, digestive, urogenital and
other tracts
 Cilia in respiratory tract
 Tears & saliva: wash away + lysozyme
o Chemical
 Enzymes: lysozyme
 Acidic environments: stomach & vagina
 Antimicrobial peptides: kill pathogens
 Sebum & sweat: sebum contains fatty acids with antimicrobial
properties
o Physical
 Coughing & sneezing: expel pathogens trapped in mucus
 Urine flow: flushed out bacteria from urinary tract

 Explain normal hematopoiesis and its role in generating various types of
immune cells.
o Multipotential Hematopoietic Stem Cell
 Common Myeloid Progenitor
 Megakaryocyte
 Thrombocytes
 Erythrocyte
 Mast cell
 Myeloblast
 Basophil
 Neutrophil
 Eosinophil
 Monocyte
- Macrophage
Figure 1: Hematopoiesi
 Common Lymphoid Progenitor
 Natural killer cell
 Small lymphocyte
 T lymphocyte
 B lymphocyte
- Plasma cell

 Identify key lymphoid organs and tissue sites where different steps of the
immune response occur.
o Primary Lymphoid Organs
 Bone Marrow
 Production of B cells, T cells, NK cells, dendritic cells,
etc.
 B cell maturation
 Thymus


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 T cell maturation
 Positive selection
 Negative selection
o Secondary Lymphoid Organs & Tissues
 Lymph nodes
 Structure
 Small, bean-shaped nodes
 Function
 Filter for lymph
 APC’s (dendritic cells & macrophages) capture
antigens and bring them to the lymph nodes to
present them to T cells etc.
 Immune response
 T and B cells encounter antigens presented by
APC’s  triggers activation  activated T cells
proliferate into cytotoxic T cells or T helper cells;
B cells into plasma cells
 Spleen
 Structure
 Red pulp
 White pulp
 Function
 Red: filters old or damaged RBC’s
 White: rich in lymphocytes, functions as lymph
node, filters blood-borne pathogens
 Immune response
 Activates B and T cells, similar to lymph nodes
 Focuses more on blood infections
 Mucosa-Associated Lymphoid Tissue (MALT)
 Structure
 Immune tissues found in mucosal surfaces
 Function
 Initiates local immune response

 Comprehend the molecular basis of immune recognition.
o Key Components
 Pattern Recognition Receptors (PRRs)
 Toll-like receptors: detect PAMPs (Pathogen-Associated
Molecular Patterns)
 LPS
 Viral RNA
 Flagellin
 Function
 Provide non-specific defense by recognizing
common microbials signatures
 Antigens & Antigen receptors
 B Cell Receptors (BCRs)
 Recognize antigens through membrane-bound
antigens (BCRs)
 BCRs can bind directly to intact antigens
-  Activates B cells
-  Differentiate into plasma cells secreting
antibodies
 T Cell Receptors (TCRs)


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 Recognize antigens presented on MHC
 CD4+ T helper cells
- MHC Class-II, found on APCs
 CD8+ Cytotoxic T cells
- MHC Class-I, found on all nucleated cells
- Directly kill infected or abnormal cells
 Major Histocompatibility Complex (MHC, HLA in
humans)
 Class I
 Found on all nucleated cells
 Present endogenous antigens (from inside the
cell, such as viral of tumor proteins)
 CD8+ cytotoxic T cells
 Class II
 Found on professional APCs
 Present exogenous antigens (outside the cell,
such as bacterial proteins:
 CD4+ helper T cells
 MHC diversity ensures a wide variety of pathogens can
be recognized
 Antigen Presentation
 APCs
 Dendritic cells
 Macrophages
 B cells
 After recognition, an APC captures a pathogen and
degrades into smaller fragments. These are loaded on
the MHC molecules and can then be recognized by T
cells
 Essential for activating T cells and the adaptive
immune system
o Key Molecular Interactions
 Antigen-antibody interaction
 Antibodies (immunoglobulins), produced by B cells,
bind specific antigens with high affinity and specificity.
 Antibodies recognize epitopes on antigens.
 Binding of antibodies can neutralize them, opsonize
them for phagocytosis, or active the complement
system (classical pathway)
 TCR-MHC-Peptide Interaction
 TCR recognize antigens presented on MHC molecules
 CD4+ (Th): MHC Class-II
 CD8+ (Tc): MHC Class-I
 After recognition, a cascade of signaling pathways
activates the t cell, which then proliferates into effector
or memory T cells
 Co-stimulatory Signals
 T cells require co-stimulatory signals, provided by the
interaction between APCs (e.g. CD80 or CD86) and
receptors on T cells (CD28)
 APCs secrete cytokines to influence the T cells to
differentiate into specific subtypes
 Th1: help macrophages suppress intracellular
infections


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- IFN-ɣ; TNF-α; IL-2; LT; GM-CSF

 Th2: help basophils, mast cells, eosinophils, and
B-cells respond to parasite infections
- IL-4; IL-5; IL-10; IL-13; TGF-β
 Th17: enhance the neutrophil response to fungal
and extracellular bacterial infections
- IL-17; IL-21; IL-22; IL-26
 Thf: help B-cells become activated, switch
isotype, and increase antibody affinity
- IL-21; IL-4; IFN-ɣ
 THαβ: provide immunity against viruses
- IFN-α; IFN-β; IL-10
 Cytokines & Chemokines
 Cytokines (e.g. interleukins & interferons) and
chemokines are signaling molecules that module
immune cell behavior
 APCs secrete cytokines
 Chemokines direct migration of immune cells to
infection sites


2. Mechanisms of Immune Response:

 Explain the mechanisms of action mediated by the innate immune system
and the acquired (or adaptive) immune system, including the key
cytokines involved.
o Innate Immune System
 Physical & Chemical barriers (MOA)
 Skin
 Mucous membranes
 Chemical secretions
 Phagocytosis (MOA)
 Macrophages and neutrophils engulf pathogens
 These cells ingest pathogens after recognizing PAMPs
 Pattern Recognition Receptors (PRRs) (MOA)
 Innate immune cells express PRRs like Toll-like
receptors that detect PAMPs
 Binding of PAMPs to PRRs triggers signaling pathway
that activate immune responses
 Inflammation (MOA)
 Inflammation triggered by innate immune system when
a pathogen invades
 Mast cells and/or macrophages release inflammatory
mediators  increase blood flow and permeability
redness, heat and swelling
 Histamines
 Cytokines
 Natural Killer (NK) cells (MOA)
 Recognize infected cells by a change in MHC Class-I
expression, like the absence of an MHC Class-I
molecule
 Can also be activated antibodies
 Release cytotoxic molecules


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