R6 - Immune Injury

Sunday, May 17, 2015

3:21 PM

Introduction

Immune system can cause tissue injury and disease.

Chapter will discuss diseases caused by too little or too much immunological activity.
Also will discuss amyloidosis - abnormal protein from Igs deposited in tissues.

The Normal Immune Response

Innate ( first line of defense) vs Adaptive Immunity ( more powerful)

Innate Immunity

Always present, ready to provide defense against microbes and to eliminate damaged cells.
Components of Innate Immunity
Epithelial barriers - block microbe entry
Mechanical barrier
Antimicrobials
Phagocytic cells - neutrophils and macrophages
Dendritic cells - APCs
NK cells - fight viruses
Mast Cells - mediators of inflammation
Plasma proteins
Complement proteins
Classic, Alternative and Lectin pathways
Cellular Receptors for Microbes, Products of Damaged Cells, and Foreign Substances
Cells that participate in innate immunity can recognize certain parts of
PAMPs
microbe that are shared among related microbes and are usually essential
for infectivity ( thus cannot be mutated to evade defense). Term?
Leukocytes also recognize stuff that falls out of injured and necrotic cells
called?
Collectively the above are called?
PRRs are located where microbes may me present: Name 3 locations

Toll Like Receptors ( TLRs)

Location

1. Plasma membrane
2. Endosome

DAMPs
PRRs

1. Plasma memb
2. Endosome - in
3. Cytoplasm - m

brane - EC microbes
ngested microbes
microbes in cytoplasm

2. Endosome - in
3. Cytoplasm - m
Toll Like Receptors ( TLRs)
Location

1. Plasma membrane
2. Endosome

Activation of 2 sets of TFs: 1. NF-kB

2. IRFs ( interferon regulatory factors)

Mutation in TLRs can cause immunodeficiency syndromes.

NOD-Like Receptors (NLRs) and the Inflammasome
Location Cytosolic
Inflammasome
IL-1
Other receptors for microbial products
C-type Lectin Receptors ( CLRs)
RIG-like Receptors (RLRs)
Mannose Receptors
Reactions of Innate Immunity
Inflammation
Antiviral Defense

Adaptive Immunity

Lymphocytes
Antibodies
There are two types of adaptive immunity:
Humoral Immunity
Cell-Mediated Immunity

Cells of the Immune System

Naive
Effector Cells
Memory Celsl
Lymphocyte Diversity
Lymphocytes specific for a large number of antigens exist before exposure to antigen, and wh
selectively activates the antigen-specific cells.
Clonal Selection
Clone
Antigen receptor diversity is generated by somatic recombination of genes that encode the re
Analysis of antigen receptor gene rearrangements is a valuble assay for detecting tumors der
T-Lymphocytes
Helper T lymphocytes stimulate B lymphocytes to make Abs and activate other leukocytes ( eg
cytotoxic T lymphocytes (CTLs) kill infected cells; and regulatory T lymphocytes limit immune
against self antigens.
The AlphaBeta ( ab) TCR recognizes peptide Ags that are presented by MHC molecules on the

ngested microbes
microbes in cytoplasm

hen an antigen enters, its

eceptor proteins.
rived from lymphocytes.

g. phagocytes) to destroy microbes;

e responses and prevent reactions

surface of APCs.

 Analysis of antigen receptor gene rearrangements is a valuble assay for detecting tumors der
T-Lymphocytes
Helper T lymphocytes stimulate B lymphocytes to make Abs and activate other leukocytes ( eg
cytotoxic T lymphocytes (CTLs) kill infected cells; and regulatory T lymphocytes limit immune
against self antigens.
The AlphaBeta ( ab) TCR recognizes peptide Ags that are presented by MHC molecules on the
MHC restriction
TCR complex
Coreceptors
CD4+ - MHC II
CD8+ - MHC I
B Lymphocytes
B lymphocytes are the only cells in the body that can make Abs ( mediators of humoral immun
Develop from bone marrow
Plasma cells
Plasmoblasts
Dendritic Cells
DCs are most important APCs for initiating T cell responses against protein Ags.
Langerhans Cells
Follicular Dendritic Cells
Macrophages
Function as APCs in T-cell activation
Can get activated by T cells to become better killers of ingested microbes.
Participate in effector phase of humoral immunity - destroy microbes coated with IgG and C3
Natural Killer Cells
Function of NK cells is to destroy irreversibly stressed and abnormal cells, such as virus infect
ADCC
Functional activity of NK cells is regulated by a balance between signals from activating and in
How do NK cells know not to kill normal cells?
IFN-gamma - activates macrophages
IL-2 and IL-15
IL-12
Innate Lymphoid Cells (ILCs)
Lack TCRs but still make cytokines
NK cells are ILCs
Early defense against infections
Recognize and eliminate stressed cells
Shape the later adaptive immune response by providing cytokines that influence differentiati

Tissues of the Immune System

Generative (primary, or central) lymphoid organs

Thymus
Bone Marrow
Peripheral (or secondary) lymphoid organs
Lymph Nodes

rived from lymphocytes.

g. phagocytes) to destroy microbes;

e responses and prevent reactions

surface of APCs.

nity)

3b.

ted cells and tumor cells.

nhibitory receptors.

ion of T lymphocytes

 Generative (primary, or central) lymphoid organs

Thymus
Bone Marrow
Peripheral (or secondary) lymphoid organs
Lymph Nodes
Spleen
Generative Lymphoid Organs
Thymus - T cells
Bone Marrow - B cells
Peripheral Lymphoid Organs
The peripheral lymphoid organs - lymph nodes, spleen, and the mucosal and cutaneous lymp
concentrate antigens, APCs and lymphocytes in a way that optimizes interactions among thes
adaptive immune responses.
Lymph Nodes
Spleen
Cutaneous and Mucosal Lymphoid Systems
Follicles
Germinal Center
Lymphocyte Recirculation
Lymphocytes constantly recirculate between tissues and home to particular sites; naive lymp
lymphoid organs where immune responses are initiated, and effector lymphocytes migrate to
inflammation.
Process is most important for T cells - plasma cells do not need to do this since they secrete A

Major Histocompatibility Complex (MHC) Molecules: The Peptide Display Sy

The function of MHC molecules is to display peptide fragments of protein antigens for recogn
Human Leukocyte Antigens (HLA)
Class I MHC molecules
Class I MHC molecules display peptides that are derived from proteins, such as viral and
in the cytoplasm and usually produced in the cell, and class I-associated peptides are re
Class I MHC restricted
Class II MHC molecules
Class II MHC molecules present antigens that are internalized into vesicles, and are typi
microbes and soluble proteins.
Class II MHC restricted
HLA Haplotype
How do MHC molecules guide combat of cytoplasmic vs extracellular microbes?
A number of autoimmune and other diseases are associated with the inheritance of particula

Cytokines: Messenger Molecules of the Immune System

Some interactions require cell to cell contact; however, many cellular interactions and functio
secreted proteins called cytokines.
Interleukins
Autocrine
Paracrine

phoid tissues - are organized to

se cells and the development of

phocytes traverse the peripheral

o sites of infection and

Abs.

ystem of Adaptive Immunity

nition by antigen specific T cells.

d tumor antigens, that are located

ecognized by CD8+ T lymphocytes.

ically derived from extracellular

ar HLA alleles.

ons of leukocytes are mediated by

Cytokines: Messenger Molecules of the Immune System

Some interactions require cell to cell contact; however, many cellular interactions and functio
secreted proteins called cytokines.
Interleukins
Autocrine
Paracrine
Endocrine
Colony Stimulating Factors

Overview of Lymphatic Activation and Immune Responses

Adaptive Immune Response Summary:

Antigen Recognition
Activation of specific lymphocytes to proliferate and differentiate into effector and mem
Elimination of antigen
Decline of response with memory cells being the long-lived survivors.
Display and Recognition of Antigens

ons of leukocytes are mediated by

mory cells